rs12719801

Positions:

• chr16-331141-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003502.4(AXIN1):​c.878+15007G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,034 control chromosomes in the GnomAD database, including 11,990 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 0.39 (11990 hom., cov: 32)
• Consequence: AXIN1 NM_003502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AXIN1	NM_003502.4	c.878+15007G>A		intron_variant		ENST00000262320.8	NP_003493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AXIN1	ENST00000262320.8	c.878+15007G>A		intron_variant		1	NM_003502.4	ENSP00000262320	A1
AXIN1	ENST00000354866.7	c.878+15007G>A		intron_variant		1		ENSP00000346935	P4
AXIN1	ENST00000461023.5	n.175+15007G>A		intron_variant, non_coding_transcript_variant		2
AXIN1	ENST00000481769.1	n.306-16458G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58747 AN: 151916 Hom.: 11968 Cov.: 32

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.387 AC: 58812 AN: 152034 Hom.: 11990 Cov.: 32 AF XY: 0.386 AC XY: 28693 AN XY: 74294

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.360

Alfa AF: 0.366 Hom.: 5691

Bravo AF: 0.383

Asia WGS AF: 0.348 AC: 1207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.8
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs12719801; hg19: chr16-381141;