rs1326934

Variant names:

• chr10-95524324-C-T
• rs1326934
• NM_001034954.3:c.-131-33204G>A

Variant summary

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

The NM_001034954.3(SORBS1):​c.-131-33204G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,086 control chromosomes in the GnomAD database, including 30,092 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 0.63 (30092 hom., cov: 33)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 12 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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORBS1	NM_001034954.3	c.-131-33204G>A		intron_variant	Intron 1 of 32	ENST00000371247.7	NP_001030126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORBS1	ENST00000371247.7	c.-131-33204G>A		intron_variant	Intron 1 of 32	5	NM_001034954.3	ENSP00000360293.2

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95412 AN: 151968 Hom.: 30066 Cov.: 33

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.592

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.628 AC: 95477 AN: 152086 Hom.: 30092 Cov.: 33 AF XY: 0.635 AC XY: 47226 AN XY: 74350

African (AFR) AF: 0.637 AC: 26425 AN: 41466

American (AMR) AF: 0.641 AC: 9791 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1916 AN: 3470

East Asian (EAS) AF: 0.728 AC: 3767 AN: 5178

South Asian (SAS) AF: 0.645 AC: 3108 AN: 4820

European-Finnish (FIN) AF: 0.730 AC: 7730 AN: 10582

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40651 AN: 67986

Other (OTH) AF: 0.592 AC: 1251 AN: 2112

Alfa AF: 0.606 Hom.: 122875

Bravo AF: 0.622

Asia WGS AF: 0.654 AC: 2271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.3
DANN	Benign	0.82
PhyloP100		-0.032
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: rs1326934; hg19: chr10-97284081;