10-95469038-C-T

Variant names:

• chr10-95469038-C-T
• rs12414693
• NM_001034954.3:c.-46+21997G>A

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+21997G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,072 control chromosomes in the GnomAD database, including 4,598 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 0.24 (4598 hom., cov: 32)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.3 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.-46+21997G>A		intron	N/A	NP_001030126.2	Q9BX66-1
	SORBS1	NM_001384452.1		c.-46+21997G>A		intron	N/A	NP_001371381.1
	SORBS1	NM_001384448.1		c.-46+21997G>A		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.-46+21997G>A		intron	N/A	ENSP00000360293.2	Q9BX66-1
	SORBS1	ENST00000371227.8	TSL:1	c.-46+21997G>A		intron	N/A	ENSP00000360271.3	Q9BX66-11
	SORBS1	ENST00000371249.6	TSL:1	c.-46+21997G>A		intron	N/A	ENSP00000360295.2	Q9BX66-10

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36894 AN: 151954 Hom.: 4600 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.243 AC: 36919 AN: 152072 Hom.: 4598 Cov.: 32 AF XY: 0.242 AC XY: 17960 AN XY: 74364

African (AFR) AF: 0.247 AC: 10229 AN: 41462

American (AMR) AF: 0.255 AC: 3901 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1053 AN: 3470

East Asian (EAS) AF: 0.0216 AC: 112 AN: 5184

South Asian (SAS) AF: 0.313 AC: 1509 AN: 4816

European-Finnish (FIN) AF: 0.209 AC: 2211 AN: 10588

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17064 AN: 67958

Other (OTH) AF: 0.249 AC: 525 AN: 2106

Alfa AF: 0.247 Hom.: 5896

Bravo AF: 0.243

Asia WGS AF: 0.177 AC: 617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.3
DANN	Benign	0.87
PhyloP100		-0.25
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: rs12414693; hg19: chr10-97228795;