chr10-95513017-T-C

Variant names:

• chr10-95513017-T-C
• rs7912249
• NM_001034954.3:c.-131-21897A>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.-131-21897A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,134 control chromosomes in the GnomAD database, including 48,915 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 0.80 (48915 hom., cov: 31)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.585
• 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 (EAS) allele frequency at 95% confidence interval = 0.956 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.-131-21897A>G		intron	N/A	NP_001030126.2	Q9BX66-1
	SORBS1	NM_001384452.1		c.-131-21897A>G		intron	N/A	NP_001371381.1
	SORBS1	NM_001384448.1		c.-131-21897A>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.-131-21897A>G		intron	N/A	ENSP00000360293.2	Q9BX66-1
	SORBS1	ENST00000371227.8	TSL:1	c.-131-21897A>G		intron	N/A	ENSP00000360271.3	Q9BX66-11
	SORBS1	ENST00000371249.6	TSL:1	c.-131-21897A>G		intron	N/A	ENSP00000360295.2	Q9BX66-10

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121646 AN: 152016 Hom.: 48875 Cov.: 31

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.917

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.791

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

GnomAD4 genome AF: 0.800 AC: 121743 AN: 152134 Hom.: 48915 Cov.: 31 AF XY: 0.799 AC XY: 59447 AN XY: 74374

African (AFR) AF: 0.822 AC: 34137 AN: 41518

American (AMR) AF: 0.824 AC: 12601 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2544 AN: 3472

East Asian (EAS) AF: 0.979 AC: 5057 AN: 5168

South Asian (SAS) AF: 0.864 AC: 4159 AN: 4816

European-Finnish (FIN) AF: 0.723 AC: 7641 AN: 10570

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52872 AN: 67988

Other (OTH) AF: 0.793 AC: 1672 AN: 2108

Alfa AF: 0.786 Hom.: 179285

Bravo AF: 0.808

Asia WGS AF: 0.912 AC: 3169 AN: 3478

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	0.50
PhyloP100		0.58
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: rs7912249; hg19: chr10-97272774;