NM_001034954.3:c.-132+5389C>G

Variant names:

• chr10-95555931-G-C
• rs10882617
• NM_001034954.3:c.-132+5389C>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.-132+5389C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,184 control chromosomes in the GnomAD database, including 2,164 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 0.16 (2164 hom., cov: 32)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.305 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.-132+5389C>G		intron	N/A	NP_001030126.2	Q9BX66-1
	SORBS1	NM_001384452.1		c.-132+5389C>G		intron	N/A	NP_001371381.1
	SORBS1	NM_001384448.1		c.-132+5389C>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.-132+5389C>G		intron	N/A	ENSP00000360293.2	Q9BX66-1
	SORBS1	ENST00000371227.8	TSL:1	c.-132+5389C>G		intron	N/A	ENSP00000360271.3	Q9BX66-11
	SORBS1	ENST00000371249.6	TSL:1	c.-132+5389C>G		intron	N/A	ENSP00000360295.2	Q9BX66-10

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24687 AN: 152066 Hom.: 2160 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.162 AC: 24710 AN: 152184 Hom.: 2164 Cov.: 32 AF XY: 0.165 AC XY: 12253 AN XY: 74404

African (AFR) AF: 0.129 AC: 5335 AN: 41504

American (AMR) AF: 0.219 AC: 3345 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 509 AN: 3472

East Asian (EAS) AF: 0.151 AC: 783 AN: 5186

South Asian (SAS) AF: 0.318 AC: 1531 AN: 4816

European-Finnish (FIN) AF: 0.138 AC: 1466 AN: 10606

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11235 AN: 68000

Other (OTH) AF: 0.155 AC: 328 AN: 2112

Alfa AF: 0.159 Hom.: 251

Bravo AF: 0.163

Asia WGS AF: 0.204 AC: 708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.62
PhyloP100		-0.036
Mutation Taster		=16/84	disease causing

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: rs10882617; hg19: chr10-97315688;