rs3736775

Variant summary

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

The NM_006363.6(SEC23B):c.1744-20T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,608,286 control chromosomes in the GnomAD database, including 125,909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9551 hom., cov: 33)

Exomes 𝑓: 0.40 ( 116358 hom. )

Consequence

SEC23B
NM_006363.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 3.50

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=-0.78).

BP6

Variant 20-18548589-T-A is Benign according to our data. Variant chr20-18548589-T-A is described in ClinVar as [Benign]. Clinvar id is 95385.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-18548589-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.442 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.1744-20T>A		intron_variant		ENST00000650089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC23B	ENST00000650089.1 linkuse as main transcript	c.1744-20T>A		intron_variant			NM_006363.6	P1

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

51797

AN:

152010

Hom.:

9552

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.314

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.419

Gnomad SAS

AF:

0.456

Gnomad FIN

AF:

0.442

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.404

Gnomad OTH

AF:

0.302

GnomAD3 exomes

AF:

0.376

AC:

94042

AN:

250294

Hom.:

18463

AF XY:

0.385

AC XY:

52125

AN XY:

135298

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.290

Gnomad ASJ exome

AF:

0.231

Gnomad EAS exome

AF:

0.427

Gnomad SAS exome

AF:

0.442

Gnomad FIN exome

AF:

0.434

Gnomad NFE exome

AF:

0.403

Gnomad OTH exome

AF:

0.365

GnomAD4 exome

AF:

0.395

AC:

575785

AN:

1456156

Hom.:

116358

Cov.:

AF XY:

0.398

AC XY:

288238

AN XY:

724686

show subpopulations

Gnomad4 AFR exome

AF:

0.208

Gnomad4 AMR exome

AF:

0.292

Gnomad4 ASJ exome

AF:

0.219

Gnomad4 EAS exome

AF:

0.362

Gnomad4 SAS exome

AF:

0.443

Gnomad4 FIN exome

AF:

0.438

Gnomad4 NFE exome

AF:

0.406

Gnomad4 OTH exome

AF:

0.383

GnomAD4 genome

AF:

0.341

AC:

51807

AN:

152130

Hom.:

9551

Cov.:

AF XY:

0.345

AC XY:

25661

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.210

Gnomad4 AMR

AF:

0.314

Gnomad4 ASJ

AF:

0.212

Gnomad4 EAS

AF:

0.418

Gnomad4 SAS

AF:

0.458

Gnomad4 FIN

AF:

0.442

Gnomad4 NFE

AF:

0.404

Gnomad4 OTH

AF:

0.301

Alfa

AF:

0.364

Hom.:

1994

Bravo

AF:

0.321

Asia WGS

AF:

0.403

AC:

1399

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 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:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Cowden syndrome 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Congenital dyserythropoietic anemia, type II

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

Cadd

Benign

4.3

Dann

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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