10-95470005-G-A

Variant names:

• chr10-95470005-G-A
• rs579342
• NM_001034954.3:c.-46+21030C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001034954.3(SORBS1):​c.-46+21030C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 152,260 control chromosomes in the GnomAD database, including 462 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 0.071 (462 hom., cov: 32)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORBS1	NM_001034954.3	c.-46+21030C>T		intron_variant	Intron 2 of 32	ENST00000371247.7	NP_001030126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORBS1	ENST00000371247.7	c.-46+21030C>T		intron_variant	Intron 2 of 32	5	NM_001034954.3	ENSP00000360293.2

Frequencies

GnomAD3 genomes AF: 0.0709 AC: 10782 AN: 152142 Hom.: 464 Cov.: 32

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.0582

Gnomad AMR AF: 0.0617

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0310

Gnomad SAS AF: 0.0733

Gnomad FIN AF: 0.0722

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0957

Gnomad OTH AF: 0.0703

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

GnomAD4 genome AF: 0.0708 AC: 10778 AN: 152260 Hom.: 462 Cov.: 32 AF XY: 0.0705 AC XY: 5246 AN XY: 74444

African (AFR) AF: 0.0331 AC: 1375 AN: 41542

American (AMR) AF: 0.0617 AC: 943 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 449 AN: 3470

East Asian (EAS) AF: 0.0310 AC: 161 AN: 5188

South Asian (SAS) AF: 0.0736 AC: 355 AN: 4826

European-Finnish (FIN) AF: 0.0722 AC: 766 AN: 10612

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0956 AC: 6504 AN: 68018

Other (OTH) AF: 0.0696 AC: 147 AN: 2112

Alfa AF: 0.0871 Hom.: 1852

Bravo AF: 0.0683

Asia WGS AF: 0.0510 AC: 178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.51
PhyloP100		0.20
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: rs579342; hg19: chr10-97229762;