chr16-288085-G-T

Variant names:

• chr16-288085-G-T
• rs200168060
• NM_003502.4:c.*37C>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.*37C>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 0.00611 in 1,612,702 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0037 (4 hom., cov: 34)
  • Exomes 𝑓: 0.0064 (39 hom.)
• Consequence: AXIN1 NM_003502.4 3_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.00

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-288085-G-T is Benign according to our data. Variant chr16-288085-G-T is described in ClinVar as [Benign]. Clinvar id is 3352842.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 560 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXIN1	NM_003502.4	c.*37C>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.*37C>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_003502.4	ENSP00000262320.3
AXIN1	ENST00000354866.7	c.*37C>A		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000346935.3
AXIN1	ENST00000461023.5	n.5695C>A		non_coding_transcript_exon_variant	Exon 8 of 8	2
AXIN1	ENST00000457798.1	c.*131C>A		downstream_gene_variant		3		ENSP00000416835.1

Frequencies

GnomAD3 genomes AF: 0.00368 AC: 560 AN: 152196 Hom.: 4 Cov.: 34

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00641

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00364 AC: 910 AN: 250240 AF XY: 0.00342

Gnomad AFR exome AF: 0.000805

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00259

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00206

Gnomad NFE exome AF: 0.00665

Gnomad OTH exome AF: 0.00343

GnomAD4 exome AF: 0.00637 AC: 9297 AN: 1460388 Hom.: 39 Cov.: 31 AF XY: 0.00607 AC XY: 4410 AN XY: 726518

African (AFR) AF: 0.000986 AC: 33 AN: 33478

American (AMR) AF: 0.00152 AC: 68 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00184 AC: 48 AN: 26132

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

South Asian (SAS) AF: 0.000243 AC: 21 AN: 86258

European-Finnish (FIN) AF: 0.00211 AC: 110 AN: 52012

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00789 AC: 8776 AN: 1111940

Other (OTH) AF: 0.00394 AC: 238 AN: 60376

GnomAD4 genome AF: 0.00368 AC: 560 AN: 152314 Hom.: 4 Cov.: 34 AF XY: 0.00352 AC XY: 262 AN XY: 74478

African (AFR) AF: 0.00125 AC: 52 AN: 41578

American (AMR) AF: 0.00288 AC: 44 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00641 AC: 436 AN: 68014

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.00409 Hom.: 0

Bravo AF: 0.00368

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

AXIN1-related disorder Benign:1

Apr 11, 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	-0.90
CADD	Benign	0.21
DANN	Benign	0.56
PhyloP100		-1.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Mutation Taster		=100/0	polymorphism

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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Other links and lift over

dbSNP: rs200168060; hg19: chr16-338085; COSMIC: COSV104574390;