10-95312115-G-T

Variant names:

• chr10-95312115-G-T
• rs9313
• NM_001034954.3:c.*2944C>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.*2944C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0678 in 152,522 control chromosomes in the GnomAD database, including 667 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 0.068 (666 hom., cov: 33)
  • Exomes 𝑓: 0.083 (1 hom.)
• Consequence: SORBS1 NM_001034954.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• Publications: 10 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORBS1	NM_001034954.3	c.*2944C>A		3_prime_UTR_variant	Exon 33 of 33	ENST00000371247.7	NP_001030126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORBS1	ENST00000371247.7	c.*2944C>A		3_prime_UTR_variant	Exon 33 of 33	5	NM_001034954.3	ENSP00000360293.2

Frequencies

GnomAD3 genomes AF: 0.0676 AC: 10278 AN: 151972 Hom.: 658 Cov.: 33

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0732

Gnomad ASJ AF: 0.0718

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0944

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0481

Gnomad OTH AF: 0.0830

GnomAD4 exome AF: 0.0833 AC: 36 AN: 432 Hom.: 1 Cov.: 0 AF XY: 0.0692 AC XY: 18 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0845 AC: 36 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0677 AC: 10304 AN: 152090 Hom.: 666 Cov.: 33 AF XY: 0.0725 AC XY: 5388 AN XY: 74350

African (AFR) AF: 0.0429 AC: 1780 AN: 41500

American (AMR) AF: 0.0741 AC: 1133 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0718 AC: 249 AN: 3470

East Asian (EAS) AF: 0.378 AC: 1949 AN: 5162

South Asian (SAS) AF: 0.140 AC: 675 AN: 4806

European-Finnish (FIN) AF: 0.0944 AC: 997 AN: 10566

Middle Eastern (MID) AF: 0.0479 AC: 14 AN: 292

European-Non Finnish (NFE) AF: 0.0481 AC: 3273 AN: 67992

Other (OTH) AF: 0.0883 AC: 186 AN: 2106

Alfa AF: 0.0502 Hom.: 280

Bravo AF: 0.0646

Asia WGS AF: 0.235 AC: 812 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.46
DANN	Benign	0.34
PhyloP100		-0.24
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: rs9313; hg19: chr10-97071872; COSMIC: COSV53359082; COSMIC: COSV53359082;