rs41309927

Positions:

chr20-18532706-G-A

Variant summary

Our verdict is Benign. Variant got -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. 15/20 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:8

Conservation

PhyloP100: 2.51

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 167666.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-18532706-G-A is described in Lovd as [Benign]. Variant chr20-18532706-G-A is described in Lovd as [Likely_benign].

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/exons	MANE	UniProt
SEC23B	NM_006363.6 linkuse as main transcript	c.1276G>A	p.Val426Ile	missense_variant	11/20	ENST00000650089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC23B	ENST00000650089.1 linkuse as main transcript	c.1276G>A	p.Val426Ile	missense_variant	11/20		NM_006363.6	P1

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

GnomAD3 exomes

AF:

0.0428

AC:

10770

AN:

251432

Hom.:

331

AF XY:

0.0441

AC XY:

5998

AN XY:

135882

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 SAS exome

AF:

0.0178

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

Gnomad4 AFR exome

AF:

0.00881

Gnomad4 AMR exome

AF:

0.0243

Gnomad4 ASJ exome

AF:

0.0506

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0178

Gnomad4 FIN exome

AF:

0.0727

Gnomad4 NFE exome

AF:

0.0549

Gnomad4 OTH exome

AF:

0.0448

GnomAD4 genome

AF:

0.0412

AC:

6275

AN:

152208

Hom.:

173

Cov.:

AF XY:

0.0423

AC XY:

3148

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.00941

Gnomad4 AMR

AF:

0.0375

Gnomad4 ASJ

AF:

0.0517

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0149

Gnomad4 FIN

AF:

0.0840

Gnomad4 NFE

AF:

0.0585

Gnomad4 OTH

AF:

0.0531

Alfa

AF:

0.0544

Hom.:

427

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:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 18, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 16, 2020	This variant is associated with the following publications: (PMID: 32641076, 27884173, 19561605, 22208203, 20981092, 22995991) -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Congenital dyserythropoietic anemia, type II

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

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

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

MutationTaster

Benign

1.0

D;D;D;D

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

Splicing

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over