dbSNP rs7076888: SORBS1:c.2128+1169G>A (chr10-95356462-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001034954.3(SORBS1):c.2128+1169G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,550,148 control chromosomes in the GnomAD database, including 241,970 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 0.56 ( 24413 hom., cov: 31)

Exomes 𝑓: 0.56 ( 217557 hom. )

Consequence

SORBS1
NM_001034954.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.183

Publications

11 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORBS1	NM_001034954.3 link	c.2128+1169G>A		intron_variant	Intron 23 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.2128+1169G>A		intron_variant	Intron 23 of 32	5	NM_001034954.3	ENSP00000360293.2		Q9BX66-1

Frequencies

GnomAD3 genomes

AF:

0.562

AC:

85388

AN:

151854

Hom.:

24389

Cov.:

show subpopulations

Gnomad AFR

AF:

0.577

Gnomad AMI

AF:

0.430

Gnomad AMR

AF:

0.656

Gnomad ASJ

AF:

0.674

Gnomad EAS

AF:

0.319

Gnomad SAS

AF:

0.607

Gnomad FIN

AF:

0.533

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.548

Gnomad OTH

AF:

0.573

GnomAD2 exomes

AF:

0.577

AC:

85911

AN:

149016

AF XY:

0.575

show subpopulations

Gnomad AFR exome

AF:

0.579

Gnomad AMR exome

AF:

0.706

Gnomad ASJ exome

AF:

0.653

Gnomad EAS exome

AF:

0.322

Gnomad FIN exome

AF:

0.531

Gnomad NFE exome

AF:

0.551

Gnomad OTH exome

AF:

0.581

GnomAD4 exome

AF:

0.555

AC:

776686

AN:

1398176

Hom.:

217557

Cov.:

102

AF XY:

0.557

AC XY:

384345

AN XY:

689594

show subpopulations

African (AFR)

AF:

0.582

AC:

18374

AN:

31596

American (AMR)

AF:

0.695

AC:

24820

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.655

AC:

16500

AN:

25180

East Asian (EAS)

AF:

0.351

AC:

12560

AN:

35734

South Asian (SAS)

AF:

0.618

AC:

48965

AN:

79234

European-Finnish (FIN)

AF:

0.530

AC:

25507

AN:

48134

Middle Eastern (MID)

AF:

0.601

AC:

3423

AN:

5698

European-Non Finnish (NFE)

AF:

0.551

AC:

594290

AN:

1078900

Other (OTH)

AF:

0.556

AC:

32247

AN:

57998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

24955

49910

74866

99821

124776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17008

34016

51024

68032

85040

<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:

0.562

AC:

85457

AN:

151972

Hom.:

24413

Cov.:

AF XY:

0.563

AC XY:

41831

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.577

AC:

23899

AN:

41422

American (AMR)

AF:

0.655

AC:

10011

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.674

AC:

2339

AN:

3472

East Asian (EAS)

AF:

0.319

AC:

1644

AN:

5148

South Asian (SAS)

AF:

0.608

AC:

2919

AN:

4804

European-Finnish (FIN)

AF:

0.533

AC:

5634

AN:

10576

Middle Eastern (MID)

AF:

0.534

AC:

156

AN:

292

European-Non Finnish (NFE)

AF:

0.548

AC:

37265

AN:

67952

Other (OTH)

AF:

0.568

AC:

1200

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1867

3734

5600

7467

9334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

724

1448

2172

2896

3620

<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:

0.555

Hom.:

76521

Bravo

AF:

0.573

Asia WGS

AF:

0.492

AC:

1713

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

0.18

PromoterAI

-0.028

Neutral

(source)

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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