NM_001290258.2:c.215C>T

Variant names:

• chr7-123616418-C-T
• rs200086727
• NM_001290258.2:c.215C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001290258.2(ASB15):​c.215C>T​(p.Ala72Val) variant causes a missense change. The variant allele was found at a frequency of 0.000028 in 1,606,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. A72S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: ASB15 NM_001290258.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.60
• Publications: 0 publications found

Genes affected

ASB15 (HGNC:19767): (ankyrin repeat and SOCS box containing 15) This gene encodes a member of the suppressor of cytokine signaling box superfamily. The proteins in this superfamily participate in the ubiquitin-proteasome system for the degradation of proteins in the cell cycle and signal transduction pathways. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ASB15-AS1 (HGNC:40904): (ASB15 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0804351).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290258.2. 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
	ASB15	NM_001290258.2	MANE Select	c.215C>T	p.Ala72Val	missense	Exon 6 of 12	NP_001277187.1	Q8WXK1
	ASB15	NM_080928.4		c.215C>T	p.Ala72Val	missense	Exon 4 of 10	NP_563616.3	A0A384NYV2
	ASB15-AS1	NR_111922.1		n.387-1018G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB15	ENST00000451215.6	TSL:2 MANE Select	c.215C>T	p.Ala72Val	missense	Exon 6 of 12	ENSP00000416433.1	Q8WXK1
	ASB15	ENST00000447789.5	TSL:1	c.215C>T	p.Ala72Val	missense	Exon 4 of 7	ENSP00000401166.1	A0A0C4DG46
	ASB15	ENST00000944024.1		c.287C>T	p.Ala96Val	missense	Exon 6 of 12	ENSP00000614083.1

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 151978 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000580

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000319 AC: 8 AN: 250868 AF XY: 0.0000295

Gnomad AFR exome AF: 0.000493

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1454902 Hom.: 0 Cov.: 33 AF XY: 0.0000152 AC XY: 11 AN XY: 724192

African (AFR) AF: 0.000571 AC: 19 AN: 33282

American (AMR) AF: 0.00 AC: 0 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26060

East Asian (EAS) AF: 0.00 AC: 0 AN: 39600

South Asian (SAS) AF: 0.00 AC: 0 AN: 86020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106018

Other (OTH) AF: 0.0000166 AC: 1 AN: 60146

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152096 Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15 AN XY: 74346

African (AFR) AF: 0.000578 AC: 24 AN: 41492

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67960

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000317 Hom.: 0

Bravo AF: 0.000181

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.0096	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.6
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.092
Sift	Benign	0.23	T
Sift4G	Benign	0.28	T
Polyphen		0.40	B
Vest4		0.43
MVP		0.58
MPC		0.15
ClinPred		0.080	T
GERP RS		5.9
Varity_R		0.15
gMVP		0.11
Mutation Taster		=83/17	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: rs200086727; hg19: chr7-123256472;