NM_003502.4:c.878+3687G>A

Variant names:

• chr16-342461-C-T
• rs370681
• NM_003502.4:c.878+3687G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003502.4(AXIN1):​c.878+3687G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,980 control chromosomes in the GnomAD database, including 17,798 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (17798 hom., cov: 32)
• Consequence: AXIN1 NM_003502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 15 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXIN1	NM_003502.4	c.878+3687G>A		intron_variant	Intron 2 of 10	ENST00000262320.8	NP_003493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXIN1	ENST00000262320.8	c.878+3687G>A		intron_variant	Intron 2 of 10	1	NM_003502.4	ENSP00000262320.3
AXIN1	ENST00000354866.7	c.878+3687G>A		intron_variant	Intron 2 of 9	1		ENSP00000346935.3
AXIN1	ENST00000461023.5	n.175+3687G>A		intron_variant	Intron 1 of 7	2
AXIN1	ENST00000481769.1	n.305+9908G>A		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72352 AN: 151862 Hom.: 17779 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.439

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.476 AC: 72412 AN: 151980 Hom.: 17798 Cov.: 32 AF XY: 0.476 AC XY: 35342 AN XY: 74264

African (AFR) AF: 0.389 AC: 16115 AN: 41456

American (AMR) AF: 0.427 AC: 6529 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1286 AN: 3472

East Asian (EAS) AF: 0.310 AC: 1602 AN: 5170

South Asian (SAS) AF: 0.553 AC: 2664 AN: 4818

European-Finnish (FIN) AF: 0.542 AC: 5723 AN: 10556

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36953 AN: 67910

Other (OTH) AF: 0.444 AC: 935 AN: 2108

Alfa AF: 0.512 Hom.: 33375

Bravo AF: 0.455

Asia WGS AF: 0.479 AC: 1666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.62
DANN	Benign	0.61
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs370681; hg19: chr16-392461;