10-95513017-T-C

Variant names:

• chr10-95513017-T-C
• rs7912249
• NM_001034954.3:c.-131-21897A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001034954.3(SORBS1):​c.-131-21897A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,134 control chromosomes in the GnomAD database, including 48,915 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 0.80 (48915 hom., cov: 31)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.585

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORBS1	NM_001034954.3	c.-131-21897A>G		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.-131-21897A>G		intron_variant	Intron 1 of 32	5	NM_001034954.3	ENSP00000360293.2

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121646 AN: 152016 Hom.: 48875 Cov.: 31

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.917

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.791

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

GnomAD4 genome AF: 0.800 AC: 121743 AN: 152134 Hom.: 48915 Cov.: 31 AF XY: 0.799 AC XY: 59447 AN XY: 74374

Gnomad4 AFR AF: 0.822

Gnomad4 AMR AF: 0.824

Gnomad4 ASJ AF: 0.733

Gnomad4 EAS AF: 0.979

Gnomad4 SAS AF: 0.864

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.778

Gnomad4 OTH AF: 0.793

Alfa AF: 0.781 Hom.: 77873

Bravo AF: 0.808

Asia WGS AF: 0.912 AC: 3169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs7912249; hg19: chr10-97272774;