NM_001034954.3:c.1572C>T

Variant names:

• chr10-95381766-G-A
• rs2274490
• NM_001034954.3:c.1572C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001034954.3(SORBS1):​c.1572C>T​(p.Asp524Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,607,052 control chromosomes in the GnomAD database, including 291,029 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 0.57 (25239 hom., cov: 32)
  • Exomes 𝑓: 0.60 (265790 hom.)
• Consequence: SORBS1 NM_001034954.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.21
• Publications: 24 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=3.21 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.665 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.1572C>T	p.Asp524Asp	synonymous	Exon 18 of 33	NP_001030126.2
	SORBS1	NM_001384452.1		c.969C>T	p.Asp323Asp	synonymous	Exon 14 of 30	NP_001371381.1
	SORBS1	NM_001384448.1		c.942C>T	p.Asp314Asp	synonymous	Exon 13 of 29	NP_001371377.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SORBS1	ENST00000371247.7	TSL:5 MANE Select	c.1572C>T	p.Asp524Asp	synonymous	Exon 18 of 33	ENSP00000360293.2
	SORBS1	ENST00000361941.7	TSL:1	c.1572C>T	p.Asp524Asp	synonymous	Exon 16 of 31	ENSP00000355136.3
	SORBS1	ENST00000371227.8	TSL:1	c.1434C>T	p.Asp478Asp	synonymous	Exon 16 of 32	ENSP00000360271.3

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86589 AN: 151912 Hom.: 25233 Cov.: 32

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.610

GnomAD2 exomes AF: 0.628 AC: 156612 AN: 249188 AF XY: 0.627

Gnomad AFR exome AF: 0.449

Gnomad AMR exome AF: 0.783

Gnomad ASJ exome AF: 0.682

Gnomad EAS exome AF: 0.639

Gnomad FIN exome AF: 0.634

Gnomad NFE exome AF: 0.594

Gnomad OTH exome AF: 0.632

GnomAD4 exome AF: 0.601 AC: 874660 AN: 1455022 Hom.: 265790 Cov.: 34 AF XY: 0.603 AC XY: 436340 AN XY: 724160

African (AFR) AF: 0.443 AC: 14747 AN: 33272

American (AMR) AF: 0.770 AC: 33868 AN: 43996

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 17908 AN: 26090

East Asian (EAS) AF: 0.684 AC: 27122 AN: 39642

South Asian (SAS) AF: 0.658 AC: 56333 AN: 85576

European-Finnish (FIN) AF: 0.635 AC: 33799 AN: 53186

Middle Eastern (MID) AF: 0.623 AC: 3581 AN: 5752

European-Non Finnish (NFE) AF: 0.588 AC: 651289 AN: 1107306

Other (OTH) AF: 0.598 AC: 36013 AN: 60202

GnomAD4 genome AF: 0.570 AC: 86631 AN: 152030 Hom.: 25239 Cov.: 32 AF XY: 0.577 AC XY: 42864 AN XY: 74324

African (AFR) AF: 0.451 AC: 18685 AN: 41426

American (AMR) AF: 0.676 AC: 10336 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2398 AN: 3468

East Asian (EAS) AF: 0.646 AC: 3344 AN: 5178

South Asian (SAS) AF: 0.658 AC: 3165 AN: 4810

European-Finnish (FIN) AF: 0.647 AC: 6839 AN: 10566

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39941 AN: 67980

Other (OTH) AF: 0.608 AC: 1282 AN: 2108

Alfa AF: 0.589 Hom.: 92554

Bravo AF: 0.567

Asia WGS AF: 0.631 AC: 2197 AN: 3478

EpiCase AF: 0.594

EpiControl AF: 0.601

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	5.8
DANN	Benign	0.51
PhyloP100		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=94/6	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: rs2274490; hg19: chr10-97141523; COSMIC: COSV53354801; COSMIC: COSV53354801;