16-288189-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 12/21 in silico tools predict 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

Publications

17 publications found

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 Gene-Disease associations (from GenCC):

caudal duplication
Inheritance: AD Classification: LIMITED Submitted by: G2P
colorectal adenoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

AXIN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 774502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1186 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003502.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AXIN1	NM_003502.4	MANE Select	c.2522G>A	p.Arg841Gln	missense	Exon 11 of 11	NP_003493.1	A0A0S2Z4R0
AXIN1	NM_181050.3		c.2414G>A	p.Arg805Gln	missense	Exon 10 of 10	NP_851393.1	O15169-2
AXIN1	NR_134879.2		n.2753G>A		non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AXIN1	ENST00000262320.8	TSL:1 MANE Select	c.2522G>A	p.Arg841Gln	missense	Exon 11 of 11	ENSP00000262320.3	O15169-1
AXIN1	ENST00000354866.7	TSL:1	c.2414G>A	p.Arg805Gln	missense	Exon 10 of 10	ENSP00000346935.3	O15169-2
AXIN1	ENST00000957925.1		c.2537G>A	p.Arg846Gln	missense	Exon 11 of 11	ENSP00000627984.1

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

GnomAD2 exomes

AF:

0.00842

AC:

2111

AN:

250678

AF XY:

0.00856

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 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

African (AFR)

AF:

0.00173

AC:

AN:

33480

American (AMR)

AF:

0.00284

AC:

127

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000153

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00182

AC:

157

AN:

86258

European-Finnish (FIN)

AF:

0.0345

AC:

1827

AN:

52936

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00980

AC:

10899

AN:

1111994

Other (OTH)

AF:

0.00768

AC:

464

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

868

1736

2604

3472

4340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

396

792

1188

1584

1980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00779

AC:

1186

AN:

152322

Hom.:

Cov.:

AF XY:

0.00850

AC XY:

633

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00142

AC:

AN:

41574

American (AMR)

AF:

0.00529

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00103

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0309

AC:

328

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0103

AC:

702

AN:

68014

Other (OTH)

AF:

0.00521

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

122

182

243

304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00863

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

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Caudal duplication;C2239176:Hepatocellular carcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

Eigen

Benign

0.15

Eigen_PC

Benign

0.034

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.0048

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.3

PhyloP100

4.9

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.1

REVEL

Benign

0.16

Sift

Benign

0.12

Sift4G

Benign

0.30

Polyphen

1.0

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

Mutation Taster

=91/9

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over