rs214252

chr16-297184-A-Gchr16-297184-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003502.4(AXIN1):c.1827T>C(p.Ala609=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,610,218 control chromosomes in the GnomAD database, including 41,284 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (5539 hom., cov: 33)
  • Exomes 𝑓: 0.21 (35745 hom.)
• Consequence: AXIN1 NM_003502.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.60

Genes affected

AXIN1 (HGNC:903): (axin 1) This gene encodes a cytoplasmic protein which contains a regulation of G-protein signaling (RGS) domain and a dishevelled and axin (DIX) domain. The encoded protein interacts with adenomatosis polyposis coli, catenin beta-1, glycogen synthase kinase 3 beta, protein phosphate 2, and itself. This protein functions as a negative regulator of the wingless-type MMTV integration site family, member 1 (WNT) signaling pathway and can induce apoptosis. The crystal structure of a portion of this protein, alone and in a complex with other proteins, has been resolved. Mutations in this gene have been associated with hepatocellular carcinoma, hepatoblastomas, ovarian endometriod adenocarcinomas, and medullablastomas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP7: Synonymous conserved (PhyloP=-5.6 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AXIN1	NM_003502.4	c.1827T>C	p.Ala609=	synonymous_variant	7/11	ENST00000262320.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AXIN1	ENST00000262320.8	c.1827T>C	p.Ala609=	synonymous_variant	7/11	1	NM_003502.4	A1
AXIN1	ENST00000354866.7	c.1827T>C	p.Ala609=	synonymous_variant	7/10	1		P4
AXIN1	ENST00000461023.5	n.1124T>C		non_coding_transcript_exon_variant	6/8	2

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38323 AN: 151968 Hom.: 5526 Cov.: 33

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0609

Gnomad SAS AF: 0.0910

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.229

GnomAD3 exomes AF: 0.189 AC: 47156 AN: 249100 Hom.: 5498 AF XY: 0.185 AC XY: 24976 AN XY: 134964

Gnomad AFR exome AF: 0.398

Gnomad AMR exome AF: 0.0992

Gnomad ASJ exome AF: 0.203

Gnomad EAS exome AF: 0.0566

Gnomad SAS exome AF: 0.0947

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.229

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.213 AC: 310991 AN: 1458132 Hom.: 35745 Cov.: 37 AF XY: 0.210 AC XY: 152543 AN XY: 725602

Gnomad4 AFR exome AF: 0.405

Gnomad4 AMR exome AF: 0.108

Gnomad4 ASJ exome AF: 0.199

Gnomad4 EAS exome AF: 0.0757

Gnomad4 SAS exome AF: 0.0967

Gnomad4 FIN exome AF: 0.212

Gnomad4 NFE exome AF: 0.226

Gnomad4 OTH exome AF: 0.206

GnomAD4 genome AF: 0.252 AC: 38378 AN: 152086 Hom.: 5539 Cov.: 33 AF XY: 0.245 AC XY: 18226 AN XY: 74330

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.0610

Gnomad4 SAS AF: 0.0919

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.226

Alfa AF: 0.229 Hom.: 5148

Bravo AF: 0.260

Asia WGS AF: 0.0990 AC: 347 AN: 3478

EpiCase AF: 0.214

EpiControl AF: 0.217

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.033
Dann	Benign	0.23

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: rs214252; hg19: chr16-347184; COSMIC: COSV51983098; COSMIC: COSV51983098;