rs533480

Variant names:

• chr10-95472448-G-A
• rs533480
• NM_001034954.3:c.-46+18587C>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+18587C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,048 control chromosomes in the GnomAD database, including 8,398 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 0.33 (8398 hom., cov: 32)
• Consequence: SORBS1 NM_001034954.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• Publications: 7 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 (AFR) allele frequency at 95% confidence interval = 0.412 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+18587C>T		intron	N/A	NP_001030126.2
	SORBS1	NM_001384452.1		c.-46+18587C>T		intron	N/A	NP_001371381.1
	SORBS1	NM_001384448.1		c.-46+18587C>T		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+18587C>T		intron	N/A	ENSP00000360293.2
	SORBS1	ENST00000371227.8	TSL:1	c.-46+18587C>T		intron	N/A	ENSP00000360271.3
	SORBS1	ENST00000371249.6	TSL:1	c.-46+18587C>T		intron	N/A	ENSP00000360295.2

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49562 AN: 151930 Hom.: 8385 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.326 AC: 49621 AN: 152048 Hom.: 8398 Cov.: 32 AF XY: 0.326 AC XY: 24218 AN XY: 74338

African (AFR) AF: 0.417 AC: 17278 AN: 41450

American (AMR) AF: 0.223 AC: 3409 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1003 AN: 3470

East Asian (EAS) AF: 0.351 AC: 1816 AN: 5174

South Asian (SAS) AF: 0.315 AC: 1520 AN: 4822

European-Finnish (FIN) AF: 0.299 AC: 3158 AN: 10552

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.299 AC: 20310 AN: 67978

Other (OTH) AF: 0.315 AC: 665 AN: 2114

Alfa AF: 0.308 Hom.: 4528

Bravo AF: 0.324

Asia WGS AF: 0.338 AC: 1173 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	0.95
DANN	Benign	0.34
PhyloP100		0.039
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: rs533480; hg19: chr10-97232205;