dbSNP rs12773574: SORBS1:c.810+26A>G (chr10-95414468-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001034954.3(SORBS1):c.810+26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0465 in 1,518,490 control chromosomes in the GnomAD database, including 1,907 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 0.039 ( 165 hom., cov: 31)

Exomes 𝑓: 0.047 ( 1742 hom. )

Consequence

SORBS1
NM_001034954.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.328

Publications

2 publications found

Variant links:

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]

SORBS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORBS1	NM_001034954.3 link	c.810+26A>G		intron_variant	Intron 9 of 32	ENST00000371247.7	NP_001030126.2	Q9BX66-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORBS1	ENST00000371247.7 link	c.810+26A>G		intron_variant	Intron 9 of 32	5	NM_001034954.3	ENSP00000360293.2		Q9BX66-1

Frequencies

GnomAD3 genomes

AF:

0.0392

AC:

5941

AN:

151704

Hom.:

165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0485

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0273

Gnomad FIN

AF:

0.0395

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0536

Gnomad OTH

AF:

0.0537

GnomAD2 exomes

AF:

0.0407

AC:

7168

AN:

175986

AF XY:

0.0425

show subpopulations

Gnomad AFR exome

AF:

0.00876

Gnomad AMR exome

AF:

0.0390

Gnomad ASJ exome

AF:

0.104

Gnomad EAS exome

AF:

0.000252

Gnomad FIN exome

AF:

0.0423

Gnomad NFE exome

AF:

0.0531

Gnomad OTH exome

AF:

0.0493

GnomAD4 exome

AF:

0.0474

AC:

64735

AN:

1366668

Hom.:

1742

Cov.:

AF XY:

0.0475

AC XY:

31822

AN XY:

669678

show subpopulations

African (AFR)

AF:

0.00961

AC:

291

AN:

30278

American (AMR)

AF:

0.0407

AC:

1192

AN:

29290

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

2013

AN:

19912

East Asian (EAS)

AF:

0.000283

AC:

AN:

38908

South Asian (SAS)

AF:

0.0277

AC:

1936

AN:

69874

European-Finnish (FIN)

AF:

0.0405

AC:

2005

AN:

49524

Middle Eastern (MID)

AF:

0.0899

AC:

478

AN:

5318

European-Non Finnish (NFE)

AF:

0.0508

AC:

54253

AN:

1067332

Other (OTH)

AF:

0.0455

AC:

2556

AN:

56232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

3070

6140

9211

12281

15351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2000

4000

6000

8000

10000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0391

AC:

5937

AN:

151822

Hom.:

165

Cov.:

AF XY:

0.0386

AC XY:

2864

AN XY:

74180

show subpopulations

African (AFR)

AF:

0.0110

AC:

454

AN:

41390

American (AMR)

AF:

0.0483

AC:

737

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

383

AN:

3464

East Asian (EAS)

AF:

0.000387

AC:

AN:

5172

South Asian (SAS)

AF:

0.0273

AC:

131

AN:

4794

European-Finnish (FIN)

AF:

0.0395

AC:

417

AN:

10546

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0537

AC:

3643

AN:

67900

Other (OTH)

AF:

0.0527

AC:

111

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

293

586

878

1171

1464

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0469

Hom.:

Bravo

AF:

0.0393

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.32

(source)

DANN

Benign

0.78

PhyloP100

-0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over