20-18530812-A-G

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.1233+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.983 in 1,604,196 control chromosomes in the GnomAD database, including 777,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.92 ( 65577 hom., cov: 29)

Exomes 𝑓: 0.99 ( 711873 hom. )

Consequence

SEC23B
NM_006363.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.177

Publications

8 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 (BayesDel_noAF=-0.9).

BP6

Variant 20-18530812-A-G is Benign according to our data. Variant chr20-18530812-A-G is described in ClinVar as Benign. ClinVar VariationId is 95379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC23B	NM_006363.6 link	c.1233+9A>G		intron_variant	Intron 10 of 19	ENST00000650089.1	NP_006354.2	Q15437

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC23B	ENST00000650089.1 link	c.1233+9A>G		intron_variant	Intron 10 of 19		NM_006363.6	ENSP00000497473.1		Q15437

Frequencies

GnomAD3 genomes

AF:

0.924

AC:

139915

AN:

151404

Hom.:

65547

Cov.:

show subpopulations

Gnomad AFR

AF:

0.746

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.961

Gnomad ASJ

AF:

0.983

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.998

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.975

Gnomad NFE

AF:

0.996

Gnomad OTH

AF:

0.944

GnomAD2 exomes

AF:

0.978

AC:

241250

AN:

246626

AF XY:

0.983

show subpopulations

Gnomad AFR exome

AF:

0.743

Gnomad AMR exome

AF:

0.982

Gnomad ASJ exome

AF:

0.982

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.996

Gnomad OTH exome

AF:

0.984

GnomAD4 exome

AF:

0.989

AC:

1437042

AN:

1452684

Hom.:

711873

Cov.:

AF XY:

0.990

AC XY:

716190

AN XY:

723238

show subpopulations

African (AFR)

AF:

0.745

AC:

24595

AN:

33026

American (AMR)

AF:

0.981

AC:

43649

AN:

44490

Ashkenazi Jewish (ASJ)

AF:

0.982

AC:

25567

AN:

26036

East Asian (EAS)

AF:

1.00

AC:

39619

AN:

39622

South Asian (SAS)

AF:

0.997

AC:

85555

AN:

85788

European-Finnish (FIN)

AF:

1.00

AC:

53067

AN:

53078

Middle Eastern (MID)

AF:

0.967

AC:

5452

AN:

5638

European-Non Finnish (NFE)

AF:

0.996

AC:

1100912

AN:

1105022

Other (OTH)

AF:

0.977

AC:

58626

AN:

59984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

606

1213

1819

2426

3032

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21480

42960

64440

85920

107400

<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:

0.924

AC:

139995

AN:

151512

Hom.:

65577

Cov.:

AF XY:

0.927

AC XY:

68584

AN XY:

74016

show subpopulations

African (AFR)

AF:

0.746

AC:

30795

AN:

41266

American (AMR)

AF:

0.961

AC:

14671

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.983

AC:

3409

AN:

3468

East Asian (EAS)

AF:

1.00

AC:

5104

AN:

5104

South Asian (SAS)

AF:

0.998

AC:

4792

AN:

4804

European-Finnish (FIN)

AF:

1.00

AC:

10338

AN:

10340

Middle Eastern (MID)

AF:

0.973

AC:

286

AN:

294

European-Non Finnish (NFE)

AF:

0.996

AC:

67700

AN:

67952

Other (OTH)

AF:

0.945

AC:

1988

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

429

858

1286

1715

2144

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<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:

0.970

Hom.:

23754

Bravo

AF:

0.912

Asia WGS

AF:

0.982

AC:

3364

AN:

3426

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

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

- -

Aug 26, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Aug 15, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 29, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Congenital dyserythropoietic anemia, type II

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

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

- -

Cowden syndrome 7

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

7.8

(source)

DANN

Benign

0.62

PhyloP100

0.18

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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