16-289499-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP6_Very_StrongBP7BS2

The NM_003502.4(AXIN1):c.2403G>A(p.Arg801Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00775 in 1,612,972 control chromosomes in the GnomAD database, including 66 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0080 ( 60 hom. )

Consequence

AXIN1
NM_003502.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.163

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP6

Variant 16-289499-C-T is Benign according to our data. Variant chr16-289499-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 771011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.163 with no splicing effect.

BS2

High AC in GnomAd4 at 780 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXIN1	NM_003502.4 link	c.2403G>A	p.Arg801Arg	synonymous_variant	Exon 10 of 11	ENST00000262320.8	NP_003493.1	O15169-1A0A0S2Z4R0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AXIN1	ENST00000262320.8 link	c.2403G>A	p.Arg801Arg	synonymous_variant	Exon 10 of 11	1	NM_003502.4	ENSP00000262320.3	O15169-1
AXIN1	ENST00000354866.7 link	c.2295G>A	p.Arg765Arg	synonymous_variant	Exon 9 of 10	1		ENSP00000346935.3	O15169-2
AXIN1	ENST00000457798.1 link	c.156G>A	p.Arg52Arg	synonymous_variant	Exon 2 of 3	3		ENSP00000416835.1	H0Y830
AXIN1	ENST00000461023.5 link	n.5472G>A		non_coding_transcript_exon_variant	Exon 7 of 8	2

Frequencies

GnomAD3 genomes

AF:

0.00512

AC:

780

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00848

Gnomad OTH

AF:

0.00670

GnomAD2 exomes

AF:

0.00517

AC:

1294

AN:

250056

AF XY:

0.00491

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.00246

Gnomad ASJ exome

AF:

0.0130

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00305

Gnomad NFE exome

AF:

0.00847

Gnomad OTH exome

AF:

0.00573

GnomAD4 exome

AF:

0.00803

AC:

11725

AN:

1460640

Hom.:

Cov.:

AF XY:

0.00790

AC XY:

5738

AN XY:

726618

show subpopulations

African (AFR)

AF:

0.00119

AC:

AN:

33480

American (AMR)

AF:

0.00246

AC:

110

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0119

AC:

310

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000151

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00295

AC:

154

AN:

52206

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00963

AC:

10714

AN:

1111994

Other (OTH)

AF:

0.00619

AC:

374

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

695

1391

2086

2782

3477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00512

AC:

780

AN:

152332

Hom.:

Cov.:

AF XY:

0.00462

AC XY:

344

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00152

AC:

AN:

41584

American (AMR)

AF:

0.00373

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00273

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00848

AC:

577

AN:

68026

Other (OTH)

AF:

0.00663

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

113

150

188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00782

Hom.:

Bravo

AF:

0.00541

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00720

EpiControl

AF:

0.00664

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

AXIN1: BP4, BP7, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Caudal duplication;C2239176:Hepatocellular carcinoma

Benign:1

Dec 29, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

AXIN1-related disorder

Benign:1

Mar 25, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

5.9

(source)

DANN

Benign

0.72

PhyloP100

0.16

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=100/0

polymorphism

(source)

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

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16-289499-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over