rs12719801

Variant names:

• chr16-331141-C-T
• rs12719801
• NM_003502.4:c.878+15007G>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+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
• Publications: 18 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003502.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXIN1	NM_003502.4	MANE Select	c.878+15007G>A		intron	N/A	NP_003493.1
	AXIN1	NM_181050.3		c.878+15007G>A		intron	N/A	NP_851393.1
	AXIN1	NR_134879.2		n.1314+15007G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXIN1	ENST00000262320.8	TSL:1 MANE Select	c.878+15007G>A		intron	N/A	ENSP00000262320.3
	AXIN1	ENST00000354866.7	TSL:1	c.878+15007G>A		intron	N/A	ENSP00000346935.3
	AXIN1	ENST00000957925.1		c.878+15007G>A		intron	N/A	ENSP00000627984.1

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

African (AFR) AF: 0.491 AC: 20336 AN: 41432

American (AMR) AF: 0.364 AC: 5551 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 985 AN: 3470

East Asian (EAS) AF: 0.154 AC: 794 AN: 5172

South Asian (SAS) AF: 0.445 AC: 2149 AN: 4824

European-Finnish (FIN) AF: 0.379 AC: 4003 AN: 10554

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23914 AN: 67996

Other (OTH) AF: 0.360 AC: 761 AN: 2112

Alfa AF: 0.366 Hom.: 6286

Bravo AF: 0.383

Asia WGS AF: 0.348 AC: 1207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.8
DANN	Benign	0.78
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12719801; hg19: chr16-381141;