14-93939148-T-C

Variant names:

• chr14-93939148-T-C
• rs368927735
• NM_001202429.2:c.1577A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001202429.2(ASB2):​c.1577A>G​(p.Asn526Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,573,786 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: ASB2 NM_001202429.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.156

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.009416312).
• BP6: Variant 14-93939148-T-C is Benign according to our data. Variant chr14-93939148-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3130166.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB2	NM_001202429.2	c.1577A>G	p.Asn526Ser	missense_variant	Exon 8 of 10	ENST00000555019.6	NP_001189358.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB2	ENST00000555019.6	c.1577A>G	p.Asn526Ser	missense_variant	Exon 8 of 10	1	NM_001202429.2	ENSP00000451575.1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152164 Hom.: 0 Cov.: 32

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: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000174 AC: 36 AN: 207112 Hom.: 0 AF XY: 0.000236 AC XY: 27 AN XY: 114358

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000638

Gnomad SAS exome AF: 0.000658

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000188

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000155 AC: 221 AN: 1421622 Hom.: 1 Cov.: 31 AF XY: 0.000180 AC XY: 126 AN XY: 701560

Gnomad4 AFR exome AF: 0.0000311

Gnomad4 AMR exome AF: 0.0000248

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000260

Gnomad4 SAS exome AF: 0.000793

Gnomad4 FIN exome AF: 0.0000199

Gnomad4 NFE exome AF: 0.000135

Gnomad4 OTH exome AF: 0.0000684

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152164 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74334

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000108 Hom.: 0

Bravo AF: 0.0000793

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000121 AC: 1

ExAC AF: 0.000210 AC: 25

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 08, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.5
DANN	Benign	0.71
DEOGEN2	Benign	0.019	.;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.73	D
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.0094	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.40	N;N;N
REVEL	Benign	0.045
Sift	Benign	0.62	T;T;T
Sift4G	Benign	0.61	T;T;.
Polyphen		0.0	.;B;.
Vest4		0.053
MVP		0.37
MPC		0.15
ClinPred		0.016	T
GERP RS		-2.5
Varity_R		0.026
gMVP		0.54

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

Other links and lift over

dbSNP: rs368927735; hg19: chr14-94405494;