Variant rs214252 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003502.4(AXIN1):c.1827T>C(p.Ala609Ala) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.60

Variant links:

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]

AXIN1 links:

AXIN1 (HGNC:):

AXIN1 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
AXIN1	NM_003502.4 linkuse as main transcript	c.1827T>C	p.Ala609Ala	synonymous_variant	7/11	ENST00000262320.8	NP_003493.1	O15169-1A0A0S2Z4R0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AXIN1	ENST00000262320.8 linkuse as main transcript	c.1827T>C	p.Ala609Ala	synonymous_variant	7/11	1	NM_003502.4	ENSP00000262320.3	O15169-1
AXIN1	ENST00000354866.7 linkuse as main transcript	c.1827T>C	p.Ala609Ala	synonymous_variant	7/10	1		ENSP00000346935.3	O15169-2
AXIN1	ENST00000461023.5 linkuse as main transcript	n.1124T>C		non_coding_transcript_exon_variant	6/8	2

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38323

AN:

151968

Hom.:

5526

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.210

AC XY:

152543

AN XY:

725602

show subpopulations

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.:

AF XY:

0.245

AC XY:

18226

AN XY:

74330

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over