rs12925669

Variant names:

• chr16-291079-G-A
• rs12925669
• NM_003502.4:c.2294+111C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-291079-G-A
• chr16-291079-G-C
• chr16-291079-G-T

Variant summary

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

The NM_003502.4(AXIN1):​c.2294+111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,003,966 control chromosomes in the GnomAD database, including 12,393 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 0.12 (1387 hom., cov: 33)
  • Exomes 𝑓: 0.16 (11006 hom.)
• Consequence: AXIN1 NM_003502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.21
• Publications: 8 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 = 0.198 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXIN1	NM_003502.4	MANE Select	c.2294+111C>T		intron	N/A	NP_003493.1	A0A0S2Z4R0
	AXIN1	NM_181050.3		c.2187-1472C>T		intron	N/A	NP_851393.1	O15169-2
	AXIN1	NR_134879.2		n.2526-1472C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXIN1	ENST00000262320.8	TSL:1 MANE Select	c.2294+111C>T		intron	N/A	ENSP00000262320.3	O15169-1
	AXIN1	ENST00000354866.7	TSL:1	c.2187-1472C>T		intron	N/A	ENSP00000346935.3	O15169-2
	AXIN1	ENST00000957925.1		c.2309+111C>T		intron	N/A	ENSP00000627984.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18208 AN: 152160 Hom.: 1386 Cov.: 33

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.156 AC: 132779 AN: 851688 Hom.: 11006 Cov.: 12 AF XY: 0.158 AC XY: 69329 AN XY: 439822

African (AFR) AF: 0.0289 AC: 609 AN: 21050

American (AMR) AF: 0.0841 AC: 2935 AN: 34896

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 3234 AN: 21724

East Asian (EAS) AF: 0.106 AC: 3507 AN: 33204

South Asian (SAS) AF: 0.203 AC: 13817 AN: 67954

European-Finnish (FIN) AF: 0.129 AC: 5984 AN: 46560

Middle Eastern (MID) AF: 0.147 AC: 556 AN: 3776

European-Non Finnish (NFE) AF: 0.165 AC: 96140 AN: 582632

Other (OTH) AF: 0.150 AC: 5997 AN: 39892

GnomAD4 genome AF: 0.120 AC: 18208 AN: 152278 Hom.: 1387 Cov.: 33 AF XY: 0.120 AC XY: 8964 AN XY: 74452

African (AFR) AF: 0.0294 AC: 1221 AN: 41562

American (AMR) AF: 0.110 AC: 1683 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 501 AN: 3472

East Asian (EAS) AF: 0.127 AC: 657 AN: 5170

South Asian (SAS) AF: 0.208 AC: 1006 AN: 4830

European-Finnish (FIN) AF: 0.132 AC: 1399 AN: 10616

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11300 AN: 68006

Other (OTH) AF: 0.129 AC: 273 AN: 2116

Alfa AF: 0.147 Hom.: 2947

Bravo AF: 0.111

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.050
DANN	Benign	0.67
PhyloP100		-3.2
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: rs12925669; hg19: chr16-341079; COSMIC: COSV51988630; COSMIC: COSV51988630;