16-288146-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_003502.4(AXIN1):c.2565C>T(p.Ile855=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00056 in 1,613,504 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00070 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00054 (2 hom.)
• Consequence: AXIN1 NM_003502.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.51

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 16-288146-G-A is Benign according to our data. Variant chr16-288146-G-A is described in ClinVar as [Benign]. Clinvar id is 721381.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.51 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AXIN1	NM_003502.4	c.2565C>T	p.Ile855=	synonymous_variant	11/11	ENST00000262320.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AXIN1	ENST00000262320.8	c.2565C>T	p.Ile855=	synonymous_variant	11/11	1	NM_003502.4	A1
AXIN1	ENST00000354866.7	c.2457C>T	p.Ile819=	synonymous_variant	10/10	1		P4
AXIN1	ENST00000461023.5	n.5634C>T		non_coding_transcript_exon_variant	8/8	2
AXIN1	ENST00000457798.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.000703 AC: 107 AN: 152194 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00452

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000889 AC: 223 AN: 250900 Hom.: 0 AF XY: 0.000839 AC XY: 114 AN XY: 135802

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00338

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00259

Gnomad NFE exome AF: 0.000927

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.000545 AC: 796 AN: 1461192 Hom.: 2 Cov.: 31 AF XY: 0.000564 AC XY: 410 AN XY: 726910

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000268

Gnomad4 ASJ exome AF: 0.00360

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00250

Gnomad4 NFE exome AF: 0.000437

Gnomad4 OTH exome AF: 0.000795

GnomAD4 genome AF: 0.000703 AC: 107 AN: 152312 Hom.: 0 Cov.: 34 AF XY: 0.000765 AC XY: 57 AN XY: 74472

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00452

Gnomad4 NFE AF: 0.000735

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000838 Hom.: 0

Bravo AF: 0.000389

EpiCase AF: 0.000600

EpiControl AF: 0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 15, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.58
Dann	Benign	0.87

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: rs150808160; hg19: chr16-338146; COSMIC: COSV104574405; COSMIC: COSV104574405;