NM_007341.3:c.232-50T>C

Variant names:

• chr21-39475085-T-C
• rs874221
• NM_007341.3:c.232-50T>C

Variant summary

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

The NM_007341.3(SH3BGR):​c.232-50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,115,488 control chromosomes in the GnomAD database, including 57,770 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 0.34 (9533 hom., cov: 32)
  • Exomes 𝑓: 0.31 (48237 hom.)
• Consequence: SH3BGR NM_007341.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 8 publications found

Genes affected

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]

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]

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 (AFR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007341.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BGR	NM_007341.3	MANE Select	c.232-50T>C		intron	N/A	NP_031367.2
	GET1-SH3BGR	NM_001317744.2		c.523-50T>C		intron	N/A	NP_001304673.1
	GET1-SH3BGR	NM_001350300.2		c.523-50T>C		intron	N/A	NP_001337229.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BGR	ENST00000333634.10	TSL:1 MANE Select	c.232-50T>C		intron	N/A	ENSP00000332513.5
	GET1-SH3BGR	ENST00000647779.1		c.523-50T>C		intron	N/A	ENSP00000497977.1
	SH3BGR	ENST00000452550.5	TSL:5	c.205-50T>C		intron	N/A	ENSP00000405675.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52070 AN: 151948 Hom.: 9525 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.321

GnomAD2 exomes AF: 0.294 AC: 61750 AN: 210064 AF XY: 0.299

Gnomad AFR exome AF: 0.445

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.327

Gnomad EAS exome AF: 0.116

Gnomad FIN exome AF: 0.389

Gnomad NFE exome AF: 0.319

Gnomad OTH exome AF: 0.286

GnomAD4 exome AF: 0.309 AC: 297880 AN: 963422 Hom.: 48237 Cov.: 12 AF XY: 0.311 AC XY: 154152 AN XY: 496184

African (AFR) AF: 0.446 AC: 10281 AN: 23056

American (AMR) AF: 0.154 AC: 5825 AN: 37788

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 7092 AN: 21752

East Asian (EAS) AF: 0.173 AC: 6382 AN: 36788

South Asian (SAS) AF: 0.318 AC: 22175 AN: 69758

European-Finnish (FIN) AF: 0.385 AC: 17736 AN: 46118

Middle Eastern (MID) AF: 0.312 AC: 1323 AN: 4238

European-Non Finnish (NFE) AF: 0.314 AC: 213645 AN: 680582

Other (OTH) AF: 0.310 AC: 13421 AN: 43342

GnomAD4 genome AF: 0.343 AC: 52103 AN: 152066 Hom.: 9533 Cov.: 32 AF XY: 0.342 AC XY: 25407 AN XY: 74324

African (AFR) AF: 0.440 AC: 18263 AN: 41488

American (AMR) AF: 0.230 AC: 3507 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1158 AN: 3470

East Asian (EAS) AF: 0.138 AC: 715 AN: 5176

South Asian (SAS) AF: 0.321 AC: 1545 AN: 4818

European-Finnish (FIN) AF: 0.396 AC: 4179 AN: 10550

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21678 AN: 67980

Other (OTH) AF: 0.322 AC: 678 AN: 2104

Alfa AF: 0.319 Hom.: 10165

Bravo AF: 0.332

Asia WGS AF: 0.231 AC: 799 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.4
DANN	Benign	0.74
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs874221; hg19: chr21-40847011;