20-18530812-A-G

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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.177

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=-0.9).
• 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/exons	MANE	UniProt
SEC23B	NM_006363.6	c.1233+9A>G		intron_variant		ENST00000650089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC23B	ENST00000650089.1	c.1233+9A>G		intron_variant			NM_006363.6	P1

Frequencies

GnomAD3 genomes AF: 0.924 AC: 139915 AN: 151404 Hom.: 65547 Cov.: 29

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

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.: 29 AF XY: 0.990 AC XY: 716190 AN XY: 723238

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.: 29 AF XY: 0.927 AC XY: 68584 AN XY: 74016

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: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)	Aug 26, 2015	- -
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:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 15, 2019	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -

Congenital dyserythropoietic anemia, type II Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
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. -

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

- -

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

Other links and lift over

dbSNP: rs6081189; hg19: chr20-18511456;