NM_003502.4:c.1019+1159A>G

Variant names:

• chr16-313384-T-C
• rs12930863
• NM_003502.4:c.1019+1159A>G

Variant summary

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

The NM_003502.4(AXIN1):​c.1019+1159A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,238 control chromosomes in the GnomAD database, including 3,578 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 0.21 (3578 hom., cov: 33)
• Consequence: AXIN1 NM_003502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.764
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXIN1	NM_003502.4	c.1019+1159A>G		intron_variant	Intron 3 of 10	ENST00000262320.8	NP_003493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXIN1	ENST00000262320.8	c.1019+1159A>G		intron_variant	Intron 3 of 10	1	NM_003502.4	ENSP00000262320.3
AXIN1	ENST00000354866.7	c.1019+1159A>G		intron_variant	Intron 3 of 9	1		ENSP00000346935.3
AXIN1	ENST00000461023.5	n.316+1159A>G		intron_variant	Intron 2 of 7	2
AXIN1	ENST00000481769.1	n.446+1159A>G		intron_variant	Intron 2 of 4	3

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31233 AN: 152120 Hom.: 3575 Cov.: 33

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.205 AC: 31268 AN: 152238 Hom.: 3578 Cov.: 33 AF XY: 0.203 AC XY: 15130 AN XY: 74432

African (AFR) AF: 0.308 AC: 12798 AN: 41522

American (AMR) AF: 0.164 AC: 2505 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 510 AN: 3472

East Asian (EAS) AF: 0.130 AC: 676 AN: 5186

South Asian (SAS) AF: 0.236 AC: 1140 AN: 4830

European-Finnish (FIN) AF: 0.132 AC: 1406 AN: 10616

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11601 AN: 67998

Other (OTH) AF: 0.197 AC: 417 AN: 2114

Alfa AF: 0.177 Hom.: 3907

Bravo AF: 0.209

Asia WGS AF: 0.206 AC: 714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.47
PhyloP100		-0.76
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: rs12930863; hg19: chr16-363384;