NM_001034954.3:c.810+1656A>G

Variant names:

• chr10-95412838-T-C
• rs1410059
• NM_001034954.3:c.810+1656A>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.810+1656A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,874 control chromosomes in the GnomAD database, including 20,891 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 0.52 (20891 hom., cov: 31)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.483
• Publications: 12 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 (SAS) allele frequency at 95% confidence interval = 0.659 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.810+1656A>G		intron	N/A	NP_001030126.2
	SORBS1	NM_001384452.1		c.346-2061A>G		intron	N/A	NP_001371381.1
	SORBS1	NM_001384448.1		c.319-2061A>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.810+1656A>G		intron	N/A	ENSP00000360293.2
	SORBS1	ENST00000361941.7	TSL:1	c.810+1656A>G		intron	N/A	ENSP00000355136.3
	SORBS1	ENST00000371227.8	TSL:1	c.810+1656A>G		intron	N/A	ENSP00000360271.3

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79074 AN: 151756 Hom.: 20865 Cov.: 31

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.521 AC: 79143 AN: 151874 Hom.: 20891 Cov.: 31 AF XY: 0.522 AC XY: 38757 AN XY: 74212

African (AFR) AF: 0.585 AC: 24195 AN: 41392

American (AMR) AF: 0.499 AC: 7619 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1906 AN: 3472

East Asian (EAS) AF: 0.596 AC: 3083 AN: 5170

South Asian (SAS) AF: 0.679 AC: 3262 AN: 4806

European-Finnish (FIN) AF: 0.445 AC: 4691 AN: 10536

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32602 AN: 67920

Other (OTH) AF: 0.543 AC: 1144 AN: 2106

Alfa AF: 0.512 Hom.: 11175

Bravo AF: 0.520

Asia WGS AF: 0.629 AC: 2184 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	2.8
DANN	Benign	0.72
PhyloP100		-0.48
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: rs1410059; hg19: chr10-97172595;