Genetic Variant NM_001040445.3:c.296G>C (chr2-238435815-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001040445.3(ASB1):c.296G>C(p.Arg99Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R99Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ASB1
NM_001040445.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.32

Publications

3 publications found

Variant links:

Genes affected

ASB1 (HGNC:16011): (ankyrin repeat and SOCS box containing 1) The protein encoded by this gene contains an ankyrin repeat sequence and SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, targeting them for ubiquitination and degradation. [provided by RefSeq, Aug 2016]

ASB1 links:

ENSG00000305185 (HGNC:):

ENSG00000305185 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040445.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB1	NM_001040445.3	MANE Select	c.296G>C	p.Arg99Pro	missense	Exon 3 of 5	NP_001035535.1	Q9Y576
	ASB1	NM_001330196.2		c.191+2120G>C		intron	N/A	NP_001317125.1	B9A047

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASB1	ENST00000264607.9	TSL:1 MANE Select	c.296G>C	p.Arg99Pro	missense	Exon 3 of 5	ENSP00000264607.4	Q9Y576
ASB1	ENST00000867386.1		c.296G>C	p.Arg99Pro	missense	Exon 3 of 5	ENSP00000537445.1
ASB1	ENST00000409297.1	TSL:5	c.191+2120G>C		intron	N/A	ENSP00000387025.1	B9A047

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251372

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000629

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Uncertain

0.082

BayesDel_noAF

Benign

-0.12

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.054

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.1

PhyloP100

1.3

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.6

REVEL

Benign

0.23

Sift

Benign

0.22

Sift4G

Benign

0.15

Polyphen

0.74

Vest4

0.70

MutPred

0.43

Gain of glycosylation at K100 (P = 0.1108)

MVP

0.83

MPC

1.4

ClinPred

0.82

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.38

gMVP

0.78

Mutation Taster

=76/24

polymorphism

(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