Genetic Variant SORBS1:c.*2944C>A (chr10-95312115-G-T) – 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.*2944C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0678 in 152,522 control chromosomes in the GnomAD database, including 667 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 0.068 ( 666 hom., cov: 33)

Exomes 𝑓: 0.083 ( 1 hom. )

Consequence

SORBS1
NM_001034954.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.244

Publications

10 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:

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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=-1.0).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 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
SORBS1	NM_001034954.3	MANE Select	c.*2944C>A	3_prime_UTR	Exon 33 of 33	NP_001030126.2
SORBS1	NM_001384452.1		c.*2944C>A	3_prime_UTR	Exon 30 of 30	NP_001371381.1
SORBS1	NM_001384448.1		c.*2944C>A	3_prime_UTR	Exon 29 of 29	NP_001371377.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SORBS1	ENST00000371247.7	TSL:5 MANE Select	c.*2944C>A	3_prime_UTR	Exon 33 of 33	ENSP00000360293.2
SORBS1	ENST00000371227.8	TSL:1	c.*2944C>A	3_prime_UTR	Exon 32 of 32	ENSP00000360271.3
SORBS1	ENST00000371249.6	TSL:1	c.*2944C>A	3_prime_UTR	Exon 25 of 25	ENSP00000360295.2

Frequencies

GnomAD3 genomes

AF:

0.0676

AC:

10278

AN:

151972

Hom.:

658

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0428

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0732

Gnomad ASJ

AF:

0.0718

Gnomad EAS

AF:

0.378

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.0944

Gnomad MID

AF:

0.0573

Gnomad NFE

AF:

0.0481

Gnomad OTH

AF:

0.0830

GnomAD4 exome

AF:

0.0833

AC:

AN:

432

Hom.:

Cov.:

AF XY:

0.0692

AC XY:

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:

0.0845

AC:

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0677

AC:

10304

AN:

152090

Hom.:

666

Cov.:

AF XY:

0.0725

AC XY:

5388

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.0429

AC:

1780

AN:

41500

American (AMR)

AF:

0.0741

AC:

1133

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0718

AC:

249

AN:

3470

East Asian (EAS)

AF:

0.378

AC:

1949

AN:

5162

South Asian (SAS)

AF:

0.140

AC:

675

AN:

4806

European-Finnish (FIN)

AF:

0.0944

AC:

997

AN:

10566

Middle Eastern (MID)

AF:

0.0479

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0481

AC:

3273

AN:

67992

Other (OTH)

AF:

0.0883

AC:

186

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

455

910

1364

1819

2274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<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:

0.0502

Hom.:

280

Bravo

AF:

0.0646

Asia WGS

AF:

0.235

AC:

812

AN:

3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.46

(source)

DANN

Benign

0.34

PhyloP100

-0.24

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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