rs7071071

Variant names:

• chr10-95479951-A-G
• rs7071071
• NM_001034954.3:c.-46+11084T>C

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+11084T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 142,646 control chromosomes in the GnomAD database, including 10,954 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 0.40 (10954 hom., cov: 25)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.970
• 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 (AMR) allele frequency at 95% confidence interval = 0.44 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.-46+11084T>C		intron	N/A	NP_001030126.2
	SORBS1	NM_001384452.1		c.-46+11084T>C		intron	N/A	NP_001371381.1
	SORBS1	NM_001384448.1		c.-46+11084T>C		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.-46+11084T>C		intron	N/A	ENSP00000360293.2
	SORBS1	ENST00000371227.8	TSL:1	c.-46+11084T>C		intron	N/A	ENSP00000360271.3
	SORBS1	ENST00000371249.6	TSL:1	c.-46+11084T>C		intron	N/A	ENSP00000360295.2

Frequencies

GnomAD3 genomes AF: 0.395 AC: 56344 AN: 142534 Hom.: 10959 Cov.: 25

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.395 AC: 56354 AN: 142646 Hom.: 10954 Cov.: 25 AF XY: 0.399 AC XY: 27544 AN XY: 68998

African (AFR) AF: 0.361 AC: 13495 AN: 37360

American (AMR) AF: 0.449 AC: 6458 AN: 14378

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1337 AN: 3356

East Asian (EAS) AF: 0.325 AC: 1473 AN: 4532

South Asian (SAS) AF: 0.448 AC: 1887 AN: 4214

European-Finnish (FIN) AF: 0.452 AC: 4219 AN: 9332

Middle Eastern (MID) AF: 0.415 AC: 117 AN: 282

European-Non Finnish (NFE) AF: 0.394 AC: 26168 AN: 66342

Other (OTH) AF: 0.395 AC: 776 AN: 1964

Alfa AF: 0.391 Hom.: 30074

Bravo AF: 0.383

Asia WGS AF: 0.323 AC: 1122 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.60
PhyloP100		-0.97
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: rs7071071; hg19: chr10-97239708; COSMIC: COSV60560957;