rs1062793

Variant names:

• chr6-79701679-A-G
• rs1062793
• NM_031469.4:c.*2170A>G

Variant summary

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

The NM_031469.4(SH3BGRL2):​c.*2170A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 147,578 control chromosomes in the GnomAD database, including 6,524 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 0.28 (6523 hom., cov: 26)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: SH3BGRL2 NM_031469.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125
• Publications: 12 publications found

Genes affected

SH3BGRL2 (HGNC:15567): (SH3 domain binding glutamate rich protein like 2) Predicted to enable SH3 domain binding activity. Located in nuclear membrane and nucleoplasm. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3BGRL2	NM_031469.4	c.*2170A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000369838.6	NP_113657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3BGRL2	ENST00000369838.6	c.*2170A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_031469.4	ENSP00000358853.4
SH3BGRL2	ENST00000718098.1	n.*2445A>G		non_coding_transcript_exon_variant	Exon 5 of 5			ENSP00000520669.1
SH3BGRL2	ENST00000718104.1	c.*2170A>G		3_prime_UTR_variant	Exon 6 of 6			ENSP00000520672.1
SH3BGRL2	ENST00000718098.1	n.*2445A>G		3_prime_UTR_variant	Exon 5 of 5			ENSP00000520669.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 41228 AN: 147474 Hom.: 6521 Cov.: 26

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.500 AC: 4 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.667 AC XY: 4 AN XY: 6

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 4 AN: 8

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.002339), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.279 AC: 41234 AN: 147570 Hom.: 6523 Cov.: 26 AF XY: 0.280 AC XY: 20032 AN XY: 71648

African (AFR) AF: 0.125 AC: 4968 AN: 39702

American (AMR) AF: 0.226 AC: 3304 AN: 14590

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1336 AN: 3448

East Asian (EAS) AF: 0.200 AC: 995 AN: 4978

South Asian (SAS) AF: 0.429 AC: 1958 AN: 4562

European-Finnish (FIN) AF: 0.392 AC: 3794 AN: 9680

Middle Eastern (MID) AF: 0.359 AC: 104 AN: 290

European-Non Finnish (NFE) AF: 0.354 AC: 23854 AN: 67398

Other (OTH) AF: 0.288 AC: 582 AN: 2020

Alfa AF: 0.331 Hom.: 14696

Bravo AF: 0.253

Asia WGS AF: 0.294 AC: 1019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.45
PhyloP100		0.13
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: rs1062793; hg19: chr6-80411396; COSMIC: COSV63964613;