NM_001034954.3:c.-131-33004C>G

Variant names:

• chr10-95524124-G-C
• rs4918944
• NM_001034954.3:c.-131-33004C>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.-131-33004C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 152,206 control chromosomes in the GnomAD database, including 683 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 0.087 (683 hom., cov: 33)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 3 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 (NFE) allele frequency at 95% confidence interval = 0.0998 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.-131-33004C>G		intron	N/A	NP_001030126.2
	SORBS1	NM_001384452.1		c.-131-33004C>G		intron	N/A	NP_001371381.1
	SORBS1	NM_001384448.1		c.-131-33004C>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.-131-33004C>G		intron	N/A	ENSP00000360293.2
	SORBS1	ENST00000371227.8	TSL:1	c.-131-33004C>G		intron	N/A	ENSP00000360271.3
	SORBS1	ENST00000371249.6	TSL:1	c.-131-33004C>G		intron	N/A	ENSP00000360295.2

Frequencies

GnomAD3 genomes AF: 0.0874 AC: 13294 AN: 152088 Hom.: 681 Cov.: 33

Gnomad AFR AF: 0.0734

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0814

Gnomad ASJ AF: 0.0597

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0834

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

GnomAD4 genome AF: 0.0874 AC: 13304 AN: 152206 Hom.: 683 Cov.: 33 AF XY: 0.0866 AC XY: 6443 AN XY: 74404

African (AFR) AF: 0.0734 AC: 3050 AN: 41538

American (AMR) AF: 0.0813 AC: 1243 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0597 AC: 207 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0137 AC: 66 AN: 4820

European-Finnish (FIN) AF: 0.153 AC: 1613 AN: 10574

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6923 AN: 68012

Other (OTH) AF: 0.0825 AC: 174 AN: 2108

Alfa AF: 0.0459 Hom.: 40

Bravo AF: 0.0822

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.38
PhyloP100		-0.059
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: rs4918944; hg19: chr10-97283881;