dbSNP rs3193970: SORBS1:c.*2808A>G (chr10-95312251-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.*2808A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,448 control chromosomes in the GnomAD database, including 11,577 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 0.39 ( 11546 hom., cov: 32)

Exomes 𝑓: 0.37 ( 31 hom. )

Consequence

SORBS1
NM_001034954.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.92

Publications

12 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=-0.5).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.423 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SORBS1	NM_001034954.3	MANE Select	c.*2808A>G	3_prime_UTR	Exon 33 of 33	NP_001030126.2	Q9BX66-1
SORBS1	NM_001384452.1		c.*2808A>G	3_prime_UTR	Exon 30 of 30	NP_001371381.1
SORBS1	NM_001384448.1		c.*2808A>G	3_prime_UTR	Exon 29 of 29	NP_001371377.1	A0A3B3IRW8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SORBS1	ENST00000371247.7	TSL:5 MANE Select	c.*2808A>G	3_prime_UTR	Exon 33 of 33	ENSP00000360293.2	Q9BX66-1
SORBS1	ENST00000371227.8	TSL:1	c.*2808A>G	3_prime_UTR	Exon 32 of 32	ENSP00000360271.3	Q9BX66-11
SORBS1	ENST00000371249.6	TSL:1	c.*2808A>G	3_prime_UTR	Exon 25 of 25	ENSP00000360295.2	Q9BX66-10

Frequencies

GnomAD3 genomes

AF:

0.386

AC:

58601

AN:

151898

Hom.:

11525

Cov.:

show subpopulations

Gnomad AFR

AF:

0.368

Gnomad AMI

AF:

0.544

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.322

Gnomad EAS

AF:

0.334

Gnomad SAS

AF:

0.339

Gnomad FIN

AF:

0.384

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.427

Gnomad OTH

AF:

0.350

GnomAD4 exome

AF:

0.370

AC:

160

AN:

432

Hom.:

Cov.:

AF XY:

0.396

AC XY:

103

AN XY:

260

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.371

AC:

158

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.386

AC:

58667

AN:

152016

Hom.:

11546

Cov.:

AF XY:

0.379

AC XY:

28190

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.368

AC:

15271

AN:

41456

American (AMR)

AF:

0.293

AC:

4472

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.322

AC:

1118

AN:

3468

East Asian (EAS)

AF:

0.334

AC:

1729

AN:

5172

South Asian (SAS)

AF:

0.339

AC:

1636

AN:

4826

European-Finnish (FIN)

AF:

0.384

AC:

4042

AN:

10534

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.427

AC:

29035

AN:

67952

Other (OTH)

AF:

0.352

AC:

744

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1854

3707

5561

7414

9268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

574

1148

1722

2296

2870

<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:

0.408

Hom.:

7460

Bravo

AF:

0.376

Asia WGS

AF:

0.351

AC:

1220

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

1.9

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over