16-288114-C-T

Variant names:

• chr16-288114-C-T
• rs111335652
• NM_003502.4:c.*8G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_003502.4(AXIN1):​c.*8G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,613,256 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 34)
  • Exomes 𝑓: 0.00013 (2 hom.)
• Consequence: AXIN1 NM_003502.4 3_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.23
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-288114-C-T is Benign according to our data. Variant chr16-288114-C-T is described in ClinVar as [Benign]. Clinvar id is 3357664.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 186 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXIN1	NM_003502.4	c.*8G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000262320.8	NP_003493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXIN1	ENST00000262320.8	c.*8G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_003502.4	ENSP00000262320.3
AXIN1	ENST00000354866.7	c.*8G>A		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000346935.3
AXIN1	ENST00000461023.5	n.5666G>A		non_coding_transcript_exon_variant	Exon 8 of 8	2
AXIN1	ENST00000457798.1	c.*102G>A		downstream_gene_variant		3		ENSP00000416835.1

Frequencies

GnomAD3 genomes AF: 0.00117 AC: 178 AN: 152218 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00424

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000271 AC: 68 AN: 250676 AF XY: 0.000184

Gnomad AFR exome AF: 0.00408

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000133 AC: 194 AN: 1460920 Hom.: 2 Cov.: 31 AF XY: 0.000109 AC XY: 79 AN XY: 726770

African (AFR) AF: 0.00439 AC: 147 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52492

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111986

Other (OTH) AF: 0.000679 AC: 41 AN: 60378

GnomAD4 genome AF: 0.00122 AC: 186 AN: 152336 Hom.: 1 Cov.: 34 AF XY: 0.00117 AC XY: 87 AN XY: 74490

African (AFR) AF: 0.00442 AC: 184 AN: 41586

American (AMR) AF: 0.000131 AC: 2 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000830 Hom.: 0

Bravo AF: 0.00113

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

AXIN1-related disorder Benign:1

Sep 17, 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	-0.81
CADD	Benign	2.2
DANN	Benign	0.69
PhyloP100		1.2
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1

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

Other links and lift over

dbSNP: rs111335652; hg19: chr16-338114;