rs7076888

Variant names:

• chr10-95356462-C-T
• rs7076888
• NM_001034954.3:c.2128+1169G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001384452.1(SORBS1):​c.2169G>A​(p.Leu723Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,550,148 control chromosomes in the GnomAD database, including 241,970 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 0.56 (24413 hom., cov: 31)
  • Exomes 𝑓: 0.56 (217557 hom.)
• Consequence: SORBS1 NM_001384452.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183
• Publications: 11 publications found

Genes affected

SORBS1 (HGNC:14565): (sorbin and SH3 domain containing 1) This gene encodes a CBL-associated protein which functions in the signaling and stimulation of insulin. Mutations in this gene may be associated with human disorders of insulin resistance. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP7: Synonymous conserved (PhyloP=0.183 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384452.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS1	NM_001034954.3	MANE Select	c.2128+1169G>A		intron	N/A	NP_001030126.2	Q9BX66-1
	SORBS1	NM_001384452.1		c.2169G>A	p.Leu723Leu	synonymous	Exon 20 of 30	NP_001371381.1
	SORBS1	NM_001384448.1		c.2142G>A	p.Leu714Leu	synonymous	Exon 19 of 29	NP_001371377.1	A0A3B3IRW8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS1	ENST00000371247.7	TSL:5 MANE Select	c.2128+1169G>A		intron	N/A	ENSP00000360293.2	Q9BX66-1
	SORBS1	ENST00000361941.7	TSL:1	c.2128+1169G>A		intron	N/A	ENSP00000355136.3	Q9BX66-1
	SORBS1	ENST00000371227.8	TSL:1	c.1990+1169G>A		intron	N/A	ENSP00000360271.3	Q9BX66-11

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85388 AN: 151854 Hom.: 24389 Cov.: 31

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.573

GnomAD2 exomes AF: 0.577 AC: 85911 AN: 149016 AF XY: 0.575

Gnomad AFR exome AF: 0.579

Gnomad AMR exome AF: 0.706

Gnomad ASJ exome AF: 0.653

Gnomad EAS exome AF: 0.322

Gnomad FIN exome AF: 0.531

Gnomad NFE exome AF: 0.551

Gnomad OTH exome AF: 0.581

GnomAD4 exome AF: 0.555 AC: 776686 AN: 1398176 Hom.: 217557 Cov.: 102 AF XY: 0.557 AC XY: 384345 AN XY: 689594

African (AFR) AF: 0.582 AC: 18374 AN: 31596

American (AMR) AF: 0.695 AC: 24820 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 16500 AN: 25180

East Asian (EAS) AF: 0.351 AC: 12560 AN: 35734

South Asian (SAS) AF: 0.618 AC: 48965 AN: 79234

European-Finnish (FIN) AF: 0.530 AC: 25507 AN: 48134

Middle Eastern (MID) AF: 0.601 AC: 3423 AN: 5698

European-Non Finnish (NFE) AF: 0.551 AC: 594290 AN: 1078900

Other (OTH) AF: 0.556 AC: 32247 AN: 57998

GnomAD4 genome AF: 0.562 AC: 85457 AN: 151972 Hom.: 24413 Cov.: 31 AF XY: 0.563 AC XY: 41831 AN XY: 74240

African (AFR) AF: 0.577 AC: 23899 AN: 41422

American (AMR) AF: 0.655 AC: 10011 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2339 AN: 3472

East Asian (EAS) AF: 0.319 AC: 1644 AN: 5148

South Asian (SAS) AF: 0.608 AC: 2919 AN: 4804

European-Finnish (FIN) AF: 0.533 AC: 5634 AN: 10576

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.548 AC: 37265 AN: 67952

Other (OTH) AF: 0.568 AC: 1200 AN: 2112

Alfa AF: 0.555 Hom.: 76521

Bravo AF: 0.573

Asia WGS AF: 0.492 AC: 1713 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.88
PhyloP100		0.18
PromoterAI		-0.028	Neutral
Mutation Taster		=99/1	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: rs7076888; hg19: chr10-97116219; COSMIC: COSV53353317; COSMIC: COSV53353317;