10-95459662-T-C

Variant names:

• chr10-95459662-T-C
• rs7899065
• NM_001034954.3:c.-45-18482A>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.-45-18482A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 151,942 control chromosomes in the GnomAD database, including 34,283 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 0.67 (34283 hom., cov: 31)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.630
• Publications: 2 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=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034954.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS1	NM_001034954.3	MANE Select	c.-45-18482A>G		intron	N/A	NP_001030126.2	Q9BX66-1
	SORBS1	NM_001384452.1		c.-45-18482A>G		intron	N/A	NP_001371381.1
	SORBS1	NM_001384448.1		c.-45-18482A>G		intron	N/A	NP_001371377.1	A0A3B3IRW8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS1	ENST00000371247.7	TSL:5 MANE Select	c.-45-18482A>G		intron	N/A	ENSP00000360293.2	Q9BX66-1
	SORBS1	ENST00000371227.8	TSL:1	c.-45-18482A>G		intron	N/A	ENSP00000360271.3	Q9BX66-11
	SORBS1	ENST00000371249.6	TSL:1	c.-45-18482A>G		intron	N/A	ENSP00000360295.2	Q9BX66-10

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101581 AN: 151824 Hom.: 34255 Cov.: 31

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.669 AC: 101665 AN: 151942 Hom.: 34283 Cov.: 31 AF XY: 0.672 AC XY: 49878 AN XY: 74270

African (AFR) AF: 0.748 AC: 30969 AN: 41410

American (AMR) AF: 0.686 AC: 10478 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2201 AN: 3470

East Asian (EAS) AF: 0.689 AC: 3559 AN: 5162

South Asian (SAS) AF: 0.798 AC: 3846 AN: 4818

European-Finnish (FIN) AF: 0.590 AC: 6211 AN: 10534

Middle Eastern (MID) AF: 0.620 AC: 181 AN: 292

European-Non Finnish (NFE) AF: 0.621 AC: 42209 AN: 67964

Other (OTH) AF: 0.664 AC: 1399 AN: 2106

Alfa AF: 0.642 Hom.: 39424

Bravo AF: 0.680

Asia WGS AF: 0.714 AC: 2480 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.70
PhyloP100		0.63
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: rs7899065; hg19: chr10-97219419;