chr20-18542289-C-T

Position:

chr20-18542289-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006363.6(SEC23B):c.1405-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0859 in 1,613,372 control chromosomes in the GnomAD database, including 8,525 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.096 ( 881 hom., cov: 33)

Exomes 𝑓: 0.085 ( 7644 hom. )

Consequence

SEC23B
NM_006363.6 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0002003

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.395

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=-0.7).

BP6

Variant 20-18542289-C-T is Benign according to our data. Variant chr20-18542289-C-T is described in ClinVar as [Benign]. Clinvar id is 95381.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 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.1405-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000650089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC23B	ENST00000650089.1 linkuse as main transcript	c.1405-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_006363.6	P1

Frequencies

GnomAD3 genomes

AF:

0.0960

AC:

14606

AN:

152074

Hom.:

875

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0967

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.0987

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0692

Gnomad OTH

AF:

0.0988

GnomAD3 exomes

AF:

0.119

AC:

29796

AN:

251296

Hom.:

2312

AF XY:

0.116

AC XY:

15718

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.0992

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.0975

Gnomad EAS exome

AF:

0.258

Gnomad SAS exome

AF:

0.156

Gnomad FIN exome

AF:

0.0958

Gnomad NFE exome

AF:

0.0711

Gnomad OTH exome

AF:

0.106

GnomAD4 exome

AF:

0.0848

AC:

123973

AN:

1461178

Hom.:

7644

Cov.:

AF XY:

0.0860

AC XY:

62525

AN XY:

726916

show subpopulations

Gnomad4 AFR exome

AF:

0.0969

Gnomad4 AMR exome

AF:

0.193

Gnomad4 ASJ exome

AF:

0.0999

Gnomad4 EAS exome

AF:

0.329

Gnomad4 SAS exome

AF:

0.154

Gnomad4 FIN exome

AF:

0.0953

Gnomad4 NFE exome

AF:

0.0648

Gnomad4 OTH exome

AF:

0.0911

GnomAD4 genome

AF:

0.0962

AC:

14639

AN:

152194

Hom.:

881

Cov.:

AF XY:

0.101

AC XY:

7486

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0968

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.103

Gnomad4 EAS

AF:

0.269

Gnomad4 SAS

AF:

0.159

Gnomad4 FIN

AF:

0.0987

Gnomad4 NFE

AF:

0.0692

Gnomad4 OTH

AF:

0.104

Alfa

AF:

0.0795

Hom.:

954

Bravo

AF:

0.101

Asia WGS

AF:

0.247

AC:

858

AN:

3478

EpiCase

AF:

0.0699

EpiControl

AF:

0.0731

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 14, 2013	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Congenital dyserythropoietic anemia, type II

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

4.7

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00020

dbscSNV1_RF

Benign

0.0020

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