rs12773574

Variant names:

• chr10-95414468-T-C
• rs12773574
• NM_001034954.3:c.810+26A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-95414468-T-C
• chr10-95414468-T-G

Variant summary

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

The NM_001034954.3(SORBS1):​c.810+26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0465 in 1,518,490 control chromosomes in the GnomAD database, including 1,907 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 0.039 (165 hom., cov: 31)
  • Exomes 𝑓: 0.047 (1742 hom.)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034954.3. 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.810+26A>G		intron	N/A	NP_001030126.2	Q9BX66-1
	SORBS1	NM_001384452.1		c.346-3691A>G		intron	N/A	NP_001371381.1
	SORBS1	NM_001384448.1		c.319-3691A>G		intron	N/A	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.810+26A>G		intron	N/A	ENSP00000360293.2	Q9BX66-1
	SORBS1	ENST00000361941.7	TSL:1	c.810+26A>G		intron	N/A	ENSP00000355136.3	Q9BX66-1
	SORBS1	ENST00000371227.8	TSL:1	c.810+26A>G		intron	N/A	ENSP00000360271.3	Q9BX66-11

Frequencies

GnomAD3 genomes AF: 0.0392 AC: 5941 AN: 151704 Hom.: 165 Cov.: 31

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0273

Gnomad FIN AF: 0.0395

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0536

Gnomad OTH AF: 0.0537

GnomAD2 exomes AF: 0.0407 AC: 7168 AN: 175986 AF XY: 0.0425

Gnomad AFR exome AF: 0.00876

Gnomad AMR exome AF: 0.0390

Gnomad ASJ exome AF: 0.104

Gnomad EAS exome AF: 0.000252

Gnomad FIN exome AF: 0.0423

Gnomad NFE exome AF: 0.0531

Gnomad OTH exome AF: 0.0493

GnomAD4 exome AF: 0.0474 AC: 64735 AN: 1366668 Hom.: 1742 Cov.: 31 AF XY: 0.0475 AC XY: 31822 AN XY: 669678

African (AFR) AF: 0.00961 AC: 291 AN: 30278

American (AMR) AF: 0.0407 AC: 1192 AN: 29290

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 2013 AN: 19912

East Asian (EAS) AF: 0.000283 AC: 11 AN: 38908

South Asian (SAS) AF: 0.0277 AC: 1936 AN: 69874

European-Finnish (FIN) AF: 0.0405 AC: 2005 AN: 49524

Middle Eastern (MID) AF: 0.0899 AC: 478 AN: 5318

European-Non Finnish (NFE) AF: 0.0508 AC: 54253 AN: 1067332

Other (OTH) AF: 0.0455 AC: 2556 AN: 56232

GnomAD4 genome AF: 0.0391 AC: 5937 AN: 151822 Hom.: 165 Cov.: 31 AF XY: 0.0386 AC XY: 2864 AN XY: 74180

African (AFR) AF: 0.0110 AC: 454 AN: 41390

American (AMR) AF: 0.0483 AC: 737 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 383 AN: 3464

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5172

South Asian (SAS) AF: 0.0273 AC: 131 AN: 4794

European-Finnish (FIN) AF: 0.0395 AC: 417 AN: 10546

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0537 AC: 3643 AN: 67900

Other (OTH) AF: 0.0527 AC: 111 AN: 2106

Alfa AF: 0.0469 Hom.: 28

Bravo AF: 0.0393

Asia WGS AF: 0.0180 AC: 64 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.32
DANN	Benign	0.78
PhyloP100		-0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12773574; hg19: chr10-97174225;