2-238433556-C-T

Variant names:

• chr2-238433556-C-T
• rs754427741
• NM_001040445.3:c.52C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001040445.3(ASB1):​c.52C>T​(p.Arg18Cys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000041 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. R18G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ASB1 NM_001040445.3 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.10
• Publications: 0 publications found

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]

ENSG00000305185 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.279895).

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.52C>T	p.Arg18Cys	missense splice_region	Exon 2 of 5	NP_001035535.1	Q9Y576
	ASB1	NM_001330196.2		c.52C>T	p.Arg18Cys	missense splice_region	Exon 2 of 4	NP_001317125.1	B9A047

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB1	ENST00000264607.9	TSL:1 MANE Select	c.52C>T	p.Arg18Cys	missense splice_region	Exon 2 of 5	ENSP00000264607.4	Q9Y576
	ASB1	ENST00000867386.1		c.52C>T	p.Arg18Cys	missense splice_region	Exon 2 of 5	ENSP00000537445.1
	ASB1	ENST00000409297.1	TSL:5	c.52C>T	p.Arg18Cys	missense splice_region	Exon 2 of 4	ENSP00000387025.1	B9A047

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251004 AF XY: 0.00000737

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: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461696 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727148

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111934

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	0.97
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.1
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.084
Sift	Benign	0.032	D
Sift4G	Uncertain	0.011	D
Polyphen		0.99	D
Vest4		0.46
MutPred		0.46		Loss of MoRF binding (P = 0.016)
MVP		0.64
MPC		1.0
ClinPred		0.58	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.55
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs754427741; hg19: chr2-239342197;