Genetic Variant SEC23B:c.1233+9A>G (chr20-18530812-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 (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 id is 95379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-18530812-A-G is described in Lovd as [Benign].

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

GnomAD3 exomes

AF:

0.978

AC:

241250

AN:

246626

Hom.:

118485

AF XY:

0.983

AC XY:

131473

AN XY:

133724

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 SAS exome

AF:

0.997

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

Gnomad4 AFR exome

AF:

0.745

Gnomad4 AMR exome

AF:

0.981

Gnomad4 ASJ exome

AF:

0.982

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.997

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.996

Gnomad4 OTH exome

AF:

0.977

GnomAD4 genome

AF:

0.924

AC:

139995

AN:

151512

Hom.:

65577

Cov.:

AF XY:

0.927

AC XY:

68584

AN XY:

74016

show subpopulations

Gnomad4 AFR

AF:

0.746

Gnomad4 AMR

AF:

0.961

Gnomad4 ASJ

AF:

0.983

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.998

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.996

Gnomad4 OTH

AF:

0.945

Alfa

AF:

0.974

Hom.:

23542

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

- -

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

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

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. -

Jul 15, 2021

Genome-Nilou Lab

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

- -

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

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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