16-288189-C-T

Position:

chr16-288189-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003502.4(AXIN1):c.2522G>A(p.Arg841Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00913 in 1,613,706 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0078 ( 11 hom., cov: 34)

Exomes 𝑓: 0.0093 ( 99 hom. )

Consequence

AXIN1
NM_003502.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.87

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047746897).

BP6

Variant 16-288189-C-T is Benign according to our data. Variant chr16-288189-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 774502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AXIN1	NM_003502.4 linkuse as main transcript	c.2522G>A	p.Arg841Gln	missense_variant	11/11	ENST00000262320.8	NP_003493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AXIN1	ENST00000262320.8 linkuse as main transcript	c.2522G>A	p.Arg841Gln	missense_variant	11/11	1	NM_003502.4	ENSP00000262320	A1	O15169-1
AXIN1	ENST00000354866.7 linkuse as main transcript	c.2414G>A	p.Arg805Gln	missense_variant	10/10	1		ENSP00000346935	P4	O15169-2
AXIN1	ENST00000461023.5 linkuse as main transcript	n.5591G>A		non_coding_transcript_exon_variant	8/8	2
AXIN1	ENST00000457798.1 linkuse as main transcript			downstream_gene_variant		3		ENSP00000416835

Frequencies

GnomAD3 genomes

AF:

0.00779

AC:

1186

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0309

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00842

AC:

2111

AN:

250678

Hom.:

AF XY:

0.00856

AC XY:

1161

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.00161

Gnomad AMR exome

AF:

0.00257

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.0345

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.00866

GnomAD4 exome

AF:

0.00927

AC:

13542

AN:

1461384

Hom.:

Cov.:

AF XY:

0.00921

AC XY:

6693

AN XY:

726984

show subpopulations

Gnomad4 AFR exome

AF:

0.00173

Gnomad4 AMR exome

AF:

0.00284

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00182

Gnomad4 FIN exome

AF:

0.0345

Gnomad4 NFE exome

AF:

0.00980

Gnomad4 OTH exome

AF:

0.00768

GnomAD4 genome

AF:

0.00779

AC:

1186

AN:

152322

Hom.:

Cov.:

AF XY:

0.00850

AC XY:

633

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00529

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.0309

Gnomad4 NFE

AF:

0.0103

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00828

Hom.:

Bravo

AF:

0.00585

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.0115

AC:

ExAC

AF:

0.00840

AC:

1020

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00916

EpiControl

AF:

0.00848

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	AXIN1: BP4, BS1, BS2 -

Caudal duplication;C2239176:Hepatocellular carcinoma

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

T;.

Eigen

Benign

0.15

Eigen_PC

Benign

0.034

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.89

D;T

MetaRNN

Benign

0.0048

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.16

Sift

Benign

0.12

T;T

Sift4G

Benign

0.30

T;T

Polyphen

1.0

D;D

Vest4

0.23

MVP

0.59

MPC

0.90

ClinPred

0.026

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.43

gMVP

0.56

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over