rs3736775

Positions:

• chr20-18548589-T-A
• chr20-18548589-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 3.50

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]

ACMG classification

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	Protein	UniProt
SEC23B	NM_006363.6	c.1744-20T>A		intron_variant		ENST00000650089.1	NP_006354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC23B	ENST00000650089.1	c.1744-20T>A		intron_variant			NM_006363.6	ENSP00000497473.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51797 AN: 152010 Hom.: 9552 Cov.: 33

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

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.: 32 AF XY: 0.398 AC XY: 288238 AN XY: 724686

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.: 33 AF XY: 0.345 AC XY: 25661 AN XY: 74378

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:10

Revision: criteria provided, multiple submitters, no conflicts

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, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

Labcorp Genetics (formerly Invitae), Labcorp

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

Other links and lift over

dbSNP: rs3736775; hg19: chr20-18529233; COSMIC: COSV52725346;