rs12925669

chr16-291079-G-Achr16-291079-G-C

Variant summary

Our verdict is Benign. Variant got -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

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 = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AXIN1	NM_003502.4	c.2294+111C>T		intron_variant		ENST00000262320.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AXIN1	ENST00000262320.8	c.2294+111C>T		intron_variant		1	NM_003502.4	A1
AXIN1	ENST00000354866.7	c.2187-1472C>T		intron_variant		1		P4
AXIN1	ENST00000457798.1	c.50-1472C>T		intron_variant		3
AXIN1	ENST00000461023.5	n.3892C>T		non_coding_transcript_exon_variant	7/8	2

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

Gnomad4 AFR exome AF: 0.0289

Gnomad4 AMR exome AF: 0.0841

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.203

Gnomad4 FIN exome AF: 0.129

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.150

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

Gnomad4 AFR AF: 0.0294

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.129

Alfa AF: 0.151 Hom.: 2455

Bravo AF: 0.111

Asia WGS AF: 0.186 AC: 646 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	0.050
Dann	Benign	0.67

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: rs12925669; hg19: chr16-341079; COSMIC: COSV51988630; COSMIC: COSV51988630;