rs2837035

Positions:

• chr21-39446453-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_146618.2(GET1-SH3BGR):​n.1195-15922A>G variant causes a intron, non coding transcript 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 NR_146618.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140

Genes affected

GET1-SH3BGR (HGNC:):

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GET1-SH3BGR	NR_146618.2	n.1195-15922A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3BGR	ENST00000380631.5	c.-100+372A>G		intron_variant		5		ENSP00000370005
SH3BGR	ENST00000380634.5	c.-100+561A>G		intron_variant		5		ENSP00000370008
SH3BGR	ENST00000380637.7	c.-100+524A>G		intron_variant		3		ENSP00000370011

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

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0913

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.145

Alfa AF: 0.161 Hom.: 4094

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2837035; hg19: chr21-40818379;