10-95362484-T-C

Variant names:

• chr10-95362484-T-C
• rs4918918
• NM_001034954.3:c.1956-4681A>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.1956-4681A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 151,946 control chromosomes in the GnomAD database, including 32,160 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 0.65 (32160 hom., cov: 31)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665
• Publications: 14 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.707 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.1956-4681A>G		intron	N/A	NP_001030126.2	Q9BX66-1
	SORBS1	NM_001384452.1		c.1353-4681A>G		intron	N/A	NP_001371381.1
	SORBS1	NM_001384448.1		c.1326-4681A>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.1956-4681A>G		intron	N/A	ENSP00000360293.2	Q9BX66-1
	SORBS1	ENST00000361941.7	TSL:1	c.1956-4681A>G		intron	N/A	ENSP00000355136.3	Q9BX66-1
	SORBS1	ENST00000371227.8	TSL:1	c.1818-4681A>G		intron	N/A	ENSP00000360271.3	Q9BX66-11

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98152 AN: 151828 Hom.: 32147 Cov.: 31

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.646 AC: 98194 AN: 151946 Hom.: 32160 Cov.: 31 AF XY: 0.648 AC XY: 48082 AN XY: 74256

African (AFR) AF: 0.657 AC: 27210 AN: 41408

American (AMR) AF: 0.718 AC: 10972 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2691 AN: 3468

East Asian (EAS) AF: 0.352 AC: 1822 AN: 5170

South Asian (SAS) AF: 0.723 AC: 3486 AN: 4822

European-Finnish (FIN) AF: 0.618 AC: 6514 AN: 10544

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.640 AC: 43475 AN: 67946

Other (OTH) AF: 0.661 AC: 1393 AN: 2108

Alfa AF: 0.644 Hom.: 10764

Bravo AF: 0.654

Asia WGS AF: 0.549 AC: 1911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.51
PhyloP100		-0.67
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: rs4918918; hg19: chr10-97122241;