10-95462907-T-C

Variant names:

• chr10-95462907-T-C
• rs554765
• NM_001034954.3:c.-45-21727A>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.-45-21727A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 152,064 control chromosomes in the GnomAD database, including 37,473 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 0.70 (37473 hom., cov: 31)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORBS1	NM_001034954.3	c.-45-21727A>G		intron_variant	Intron 2 of 32	ENST00000371247.7	NP_001030126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORBS1	ENST00000371247.7	c.-45-21727A>G		intron_variant	Intron 2 of 32	5	NM_001034954.3	ENSP00000360293.2

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106119 AN: 151946 Hom.: 37431 Cov.: 31

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.691

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

GnomAD4 genome AF: 0.699 AC: 106217 AN: 152064 Hom.: 37473 Cov.: 31 AF XY: 0.699 AC XY: 51996 AN XY: 74344

African (AFR) AF: 0.806 AC: 33433 AN: 41502

American (AMR) AF: 0.707 AC: 10791 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2247 AN: 3470

East Asian (EAS) AF: 0.688 AC: 3557 AN: 5170

South Asian (SAS) AF: 0.804 AC: 3864 AN: 4808

European-Finnish (FIN) AF: 0.604 AC: 6381 AN: 10568

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43641 AN: 67958

Other (OTH) AF: 0.690 AC: 1457 AN: 2112

Alfa AF: 0.674 Hom.: 4480

Bravo AF: 0.711

Asia WGS AF: 0.722 AC: 2509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.38
DANN	Benign	0.48
PhyloP100		-0.48
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: rs554765; hg19: chr10-97222664;