rs7071071

Positions:

• chr10-95479951-A-G

Variant summary

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

The NM_001034954.3(SORBS1):​c.-46+11084T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 142,646 control chromosomes in the GnomAD database, including 10,954 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 0.40 (10954 hom., cov: 25)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.970

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SORBS1	NM_001034954.3	c.-46+11084T>C		intron_variant		ENST00000371247.7	NP_001030126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORBS1	ENST00000371247.7	c.-46+11084T>C		intron_variant		5	NM_001034954.3	ENSP00000360293	P3

Frequencies

GnomAD3 genomes AF: 0.395 AC: 56344 AN: 142534 Hom.: 10959 Cov.: 25

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.395 AC: 56354 AN: 142646 Hom.: 10954 Cov.: 25 AF XY: 0.399 AC XY: 27544 AN XY: 68998

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.395

Alfa AF: 0.392 Hom.: 19922

Bravo AF: 0.383

Asia WGS AF: 0.323 AC: 1122 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.60

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: rs7071071; hg19: chr10-97239708; COSMIC: COSV60560957;