chr21-39446453-A-G

Variant names:

• chr21-39446453-A-G
• rs2837035
• ENST00000647779.1:c.337-15922A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000647779.1(GET1-SH3BGR):​c.337-15922A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,132 control chromosomes in the GnomAD database, including 2,059 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2059 hom., cov: 32)
• Consequence: GET1-SH3BGR ENST00000647779.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140
• Publications: 6 publications found

Genes affected

GET1-SH3BGR (HGNC:54635): (GET1-SH3BGR readthrough) This locus represents naturally occurring readthrough transcription between the neighboring WRB (tryptophan rich basic protein) and SH3BGR (SH3 domain binding glutamate-rich protein) genes on chromosome 21. Readthrough transcripts may encode fusion proteins that shares sequence identity with each individual gene product. [provided by RefSeq, Apr 2017]

SH3BGR (HGNC:10822): (SH3 domain binding glutamate rich protein) Predicted to enable SH3 domain binding activity. Predicted to be involved in protein-containing complex assembly. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GET1-SH3BGR	NM_001317744.2	c.337-15922A>G		intron_variant	Intron 3 of 8		NP_001304673.1
GET1-SH3BGR	NM_001350300.2	c.337-15922A>G		intron_variant	Intron 3 of 6		NP_001337229.1
SH3BGR	NM_001001713.1	c.-100+524A>G		intron_variant	Intron 1 of 6		NP_001001713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GET1-SH3BGR	ENST00000647779.1	c.337-15922A>G		intron_variant	Intron 3 of 8			ENSP00000497977.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23643 AN: 152014 Hom.: 2058 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.0915

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.147

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.156 AC: 23658 AN: 152132 Hom.: 2059 Cov.: 32 AF XY: 0.161 AC XY: 11948 AN XY: 74362

African (AFR) AF: 0.126 AC: 5213 AN: 41518

American (AMR) AF: 0.0913 AC: 1397 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 543 AN: 3470

East Asian (EAS) AF: 0.124 AC: 640 AN: 5174

South Asian (SAS) AF: 0.157 AC: 754 AN: 4816

European-Finnish (FIN) AF: 0.298 AC: 3152 AN: 10566

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11435 AN: 67972

Other (OTH) AF: 0.145 AC: 307 AN: 2110

Alfa AF: 0.160 Hom.: 8593

Bravo AF: 0.139

Asia WGS AF: 0.128 AC: 445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.8
DANN	Benign	0.64
PhyloP100		0.014
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2837035; hg19: chr21-40818379;