rs7900095

Variant names:

• chr10-95359292-T-C
• rs7900095
• NM_001034954.3:c.1956-1489A>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.1956-1489A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,112 control chromosomes in the GnomAD database, including 31,474 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 0.64 (31474 hom., cov: 33)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.702 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS1	NM_001034954.3	MANE Select	c.1956-1489A>G		intron	N/A	NP_001030126.2
	SORBS1	NM_001384452.1		c.1353-1489A>G		intron	N/A	NP_001371381.1
	SORBS1	NM_001384448.1		c.1326-1489A>G		intron	N/A	NP_001371377.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS1	ENST00000371247.7	TSL:5 MANE Select	c.1956-1489A>G		intron	N/A	ENSP00000360293.2
	SORBS1	ENST00000361941.7	TSL:1	c.1956-1489A>G		intron	N/A	ENSP00000355136.3
	SORBS1	ENST00000371227.8	TSL:1	c.1818-1489A>G		intron	N/A	ENSP00000360271.3

Frequencies

GnomAD3 genomes AF: 0.638 AC: 97034 AN: 151992 Hom.: 31461 Cov.: 33

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.638 AC: 97078 AN: 152112 Hom.: 31474 Cov.: 33 AF XY: 0.637 AC XY: 47400 AN XY: 74364

African (AFR) AF: 0.674 AC: 27963 AN: 41496

American (AMR) AF: 0.713 AC: 10900 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2664 AN: 3470

East Asian (EAS) AF: 0.348 AC: 1801 AN: 5170

South Asian (SAS) AF: 0.703 AC: 3381 AN: 4812

European-Finnish (FIN) AF: 0.570 AC: 6033 AN: 10578

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

European-Non Finnish (NFE) AF: 0.623 AC: 42349 AN: 67978

Other (OTH) AF: 0.655 AC: 1385 AN: 2114

Alfa AF: 0.640 Hom.: 84313

Bravo AF: 0.650

Asia WGS AF: 0.540 AC: 1879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.8
DANN	Benign	0.45
PhyloP100		-0.015
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: rs7900095; hg19: chr10-97119049;