rs41309927

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006363.6(SEC23B):c.1276G>A(p.Val426Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0486 in 1,613,190 control chromosomes in the GnomAD database, including 2,222 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 173 hom., cov: 33)

Exomes 𝑓: 0.049 ( 2049 hom. )

Consequence

SEC23B
NM_006363.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.51

Publications

27 publications found

Variant links:

Genes affected

SEC23B (HGNC:10702): (SEC23 homolog B, COPII coat complex component) The protein encoded by this gene is a member of the SEC23 subfamily of the SEC23/SEC24 family, which is involved in vesicle trafficking. The encoded protein has similarity to yeast Sec23p component of COPII. COPII is the coat protein complex responsible for vesicle budding from the ER. The function of this gene product has been implicated in cargo selection and concentration. Multiple alternatively spliced transcript variants have been identified in this gene. [provided by RefSeq, Feb 2010]

SEC23B Gene-Disease associations (from GenCC):

congenital dyserythropoietic anemia type 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Laboratory for Molecular Medicine, G2P
Cowden disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Cowden syndrome 7
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
congenital dyserythropoietic anemia
Inheritance: AR Classification: LIMITED Submitted by: Genomics England PanelApp

SEC23B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046108663).

BP6

Variant 20-18532706-G-A is Benign according to our data. Variant chr20-18532706-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 167666.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.057 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC23B	NM_006363.6 link	c.1276G>A	p.Val426Ile	missense_variant	Exon 11 of 20	ENST00000650089.1	NP_006354.2	Q15437

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC23B	ENST00000650089.1 link	c.1276G>A	p.Val426Ile	missense_variant	Exon 11 of 20		NM_006363.6	ENSP00000497473.1		Q15437

Frequencies

GnomAD3 genomes

AF:

0.0413

AC:

6277

AN:

152090

Hom.:

172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00944

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.0374

Gnomad ASJ

AF:

0.0517

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0149

Gnomad FIN

AF:

0.0840

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0585

Gnomad OTH

AF:

0.0537

GnomAD2 exomes

AF:

0.0428

AC:

10770

AN:

251432

AF XY:

0.0441

show subpopulations

Gnomad AFR exome

AF:

0.00744

Gnomad AMR exome

AF:

0.0228

Gnomad ASJ exome

AF:

0.0495

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0770

Gnomad NFE exome

AF:

0.0600

Gnomad OTH exome

AF:

0.0523

GnomAD4 exome

AF:

0.0494

AC:

72195

AN:

1460982

Hom.:

2049

Cov.:

AF XY:

0.0490

AC XY:

35601

AN XY:

726832

show subpopulations

African (AFR)

AF:

0.00881

AC:

295

AN:

33468

American (AMR)

AF:

0.0243

AC:

1085

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0506

AC:

1323

AN:

26122

East Asian (EAS)

AF:

0.000101

AC:

AN:

39694

South Asian (SAS)

AF:

0.0178

AC:

1534

AN:

86244

European-Finnish (FIN)

AF:

0.0727

AC:

3883

AN:

53398

Middle Eastern (MID)

AF:

0.0661

AC:

381

AN:

5766

European-Non Finnish (NFE)

AF:

0.0549

AC:

60988

AN:

1111198

Other (OTH)

AF:

0.0448

AC:

2702

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

3380

6761

10141

13522

16902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2042

4084

6126

8168

10210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0412

AC:

6275

AN:

152208

Hom.:

173

Cov.:

AF XY:

0.0423

AC XY:

3148

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.00941

AC:

391

AN:

41546

American (AMR)

AF:

0.0375

AC:

573

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0517

AC:

179

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.0149

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0840

AC:

888

AN:

10568

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0585

AC:

3981

AN:

68004

Other (OTH)

AF:

0.0531

AC:

112

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

320

639

959

1278

1598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0521

Hom.:

763

Bravo

AF:

0.0365

TwinsUK

AF:

0.0515

AC:

191

ALSPAC

AF:

0.0506

AC:

195

ESP6500AA

AF:

0.00885

AC:

ESP6500EA

AF:

0.0612

AC:

526

ExAC

AF:

0.0431

AC:

5228

Asia WGS

AF:

0.00953

AC:

AN:

3478

EpiCase

AF:

0.0606

EpiControl

AF:

0.0652

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 18, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 16, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 32641076, 27884173, 19561605, 22208203, 20981092, 22995991) -

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 18, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital dyserythropoietic anemia, type II;C4225179:Cowden syndrome 7

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital dyserythropoietic anemia, type II

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.015

T;T;T;.;T;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

.;.;.;D;.;D

MetaRNN

Benign

0.0046

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.92

L;L;L;.;L;L

PhyloP100

2.5

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.21

N;N;N;.;.;N

REVEL

Benign

0.12

Sift

Benign

0.34

T;T;T;.;.;T

Sift4G

Benign

0.49

T;T;T;.;.;T

Polyphen

0.0

B;B;B;.;B;B

Vest4

0.064

MPC

0.13

ClinPred

0.0043

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.019

gMVP

0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over