16-322597-A-G

Variant names:

• chr16-322597-A-G
• rs3916990
• NM_003502.4:c.879-7914T>C

Variant summary

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

The NM_003502.4(AXIN1):​c.879-7914T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,078 control chromosomes in the GnomAD database, including 6,993 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 0.28 (6993 hom., cov: 32)
• Consequence: AXIN1 NM_003502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458
• Publications: 17 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXIN1	NM_003502.4	c.879-7914T>C		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.879-7914T>C		intron_variant	Intron 2 of 10	1	NM_003502.4	ENSP00000262320.3
AXIN1	ENST00000354866.7	c.879-7914T>C		intron_variant	Intron 2 of 9	1		ENSP00000346935.3
AXIN1	ENST00000461023.5	n.176-7914T>C		intron_variant	Intron 1 of 7	2
AXIN1	ENST00000481769.1	n.306-7914T>C		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43296 AN: 151960 Hom.: 6991 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.285 AC: 43313 AN: 152078 Hom.: 6993 Cov.: 32 AF XY: 0.288 AC XY: 21393 AN XY: 74340

African (AFR) AF: 0.135 AC: 5593 AN: 41504

American (AMR) AF: 0.314 AC: 4796 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 862 AN: 3470

East Asian (EAS) AF: 0.201 AC: 1041 AN: 5188

South Asian (SAS) AF: 0.362 AC: 1739 AN: 4802

European-Finnish (FIN) AF: 0.382 AC: 4042 AN: 10576

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24369 AN: 67946

Other (OTH) AF: 0.278 AC: 585 AN: 2108

Alfa AF: 0.330 Hom.: 24906

Bravo AF: 0.267

Asia WGS AF: 0.254 AC: 880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.35
PhyloP100		-0.46
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: rs3916990; hg19: chr16-372597;