2-238433556-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001040445.3(ASB1):​c.52C>G​(p.Arg18Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000744 in 1,613,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R18H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ASB1
NM_001040445.3 missense, splice_region

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.10
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22461).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASB1NM_001040445.3 linkc.52C>G p.Arg18Gly missense_variant, splice_region_variant Exon 2 of 5 ENST00000264607.9 NP_001035535.1 Q9Y576
ASB1NM_001330196.2 linkc.52C>G p.Arg18Gly missense_variant, splice_region_variant Exon 2 of 4 NP_001317125.1 B9A047

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ASB1ENST00000264607.9 linkc.52C>G p.Arg18Gly missense_variant, splice_region_variant Exon 2 of 5 1 NM_001040445.3 ENSP00000264607.4 Q9Y576

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.000478
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461696
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
727148
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000719
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000151

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 26, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.52C>G (p.R18G) alteration is located in exon 2 (coding exon 2) of the ASB1 gene. This alteration results from a C to G substitution at nucleotide position 52, causing the arginine (R) at amino acid position 18 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.096
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
22
DANN
Benign
0.96
DEOGEN2
Benign
0.25
T;T
Eigen
Benign
-0.12
Eigen_PC
Benign
0.030
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.22
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N;.
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.024
Sift
Benign
0.19
T;T
Sift4G
Benign
0.081
T;T
Polyphen
0.36
B;.
Vest4
0.41
MutPred
0.43
Loss of MoRF binding (P = 0.0275);Loss of MoRF binding (P = 0.0275);
MVP
0.58
MPC
0.66
ClinPred
0.75
D
GERP RS
4.3
Varity_R
0.18
gMVP
0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs754427741; hg19: chr2-239342197; API