rs3916990

Positions:

• chr16-322597-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	Protein	UniProt
AXIN1	NM_003502.4	c.879-7914T>C		intron_variant		ENST00000262320.8	NP_003493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AXIN1	ENST00000262320.8	c.879-7914T>C		intron_variant		1	NM_003502.4	ENSP00000262320	A1
AXIN1	ENST00000354866.7	c.879-7914T>C		intron_variant		1		ENSP00000346935	P4
AXIN1	ENST00000461023.5	n.176-7914T>C		intron_variant, non_coding_transcript_variant		2
AXIN1	ENST00000481769.1	n.306-7914T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.278

Alfa AF: 0.336 Hom.: 12095

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

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: rs3916990; hg19: chr16-372597;