14-93937798-G-C

Variant names:

• chr14-93937798-G-C
• rs146138244
• NM_001202429.2:c.1671C>G

Variant summary

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

The NM_001202429.2(ASB2):​c.1671C>G​(p.Ile557Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000472 in 1,611,698 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 (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: ASB2 NM_001202429.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.34
• Publications: 3 publications found

Genes affected

ASB2 (HGNC:16012): (ankyrin repeat and SOCS box containing 2) This gene encodes a member of the ankyrin repeat and SOCS box-containing (ASB) protein family. These proteins play a role in protein degradation by coupling suppressor of cytokine signalling (SOCS) proteins with the elongin BC complex. The encoded protein is a subunit of a multimeric E3 ubiquitin ligase complex that mediates the degradation of actin-binding proteins. This gene plays a role in retinoic acid-induced growth inhibition and differentiation of myeloid leukemia cells. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.08997947).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001202429.2. 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
	ASB2	NM_001202429.2	MANE Select	c.1671C>G	p.Ile557Met	missense	Exon 9 of 10	NP_001189358.1	Q96Q27-2
	ASB2	NM_016150.5		c.1527C>G	p.Ile509Met	missense	Exon 7 of 8	NP_057234.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB2	ENST00000555019.6	TSL:1 MANE Select	c.1671C>G	p.Ile557Met	missense	Exon 9 of 10	ENSP00000451575.1	Q96Q27-2
	ASB2	ENST00000315988.8	TSL:1	c.1527C>G	p.Ile509Met	missense	Exon 7 of 8	ENSP00000320675.4	Q96Q27-1
	ASB2	ENST00000968954.1		c.1746C>G	p.Ile582Met	missense	Exon 9 of 10	ENSP00000639013.1

Frequencies

GnomAD3 genomes AF: 0.000276 AC: 42 AN: 152178 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000941

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000677 AC: 17 AN: 251108 AF XY: 0.0000368

Gnomad AFR exome AF: 0.000924

Gnomad AMR exome AF: 0.0000579

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: 0.0000233 AC: 34 AN: 1459402 Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18 AN XY: 725504

African (AFR) AF: 0.000807 AC: 27 AN: 33458

American (AMR) AF: 0.0000448 AC: 2 AN: 44686

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39610

South Asian (SAS) AF: 0.00 AC: 0 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109980

Other (OTH) AF: 0.0000830 AC: 5 AN: 60256

GnomAD4 genome AF: 0.000276 AC: 42 AN: 152296 Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19 AN XY: 74472

African (AFR) AF: 0.000938 AC: 39 AN: 41560

American (AMR) AF: 0.000196 AC: 3 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000287

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000906 AC: 11

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	Uncertain	0.45
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.14	N
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.090	T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		-1.3
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.49
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.76
MVP		0.59
MPC		0.71
ClinPred		0.26	T
GERP RS		-1.7
Varity_R		0.47
gMVP		0.80
Mutation Taster		=76/24	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: rs146138244; hg19: chr14-94404144; COSMIC: COSV60114913; COSMIC: COSV60114913;