rs12921862

Variant names:

• chr16-331927-C-A
• rs12921862
• NM_003502.4:c.878+14221G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-331927-C-A
• chr16-331927-C-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.878+14221G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,138 control chromosomes in the GnomAD database, including 2,655 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 0.18 (2655 hom., cov: 33)
• Consequence: AXIN1 NM_003502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.810
• Publications: 15 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXIN1	NM_003502.4	c.878+14221G>T		intron_variant	Intron 2 of 10	ENST00000262320.8	NP_003493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXIN1	ENST00000262320.8	c.878+14221G>T		intron_variant	Intron 2 of 10	1	NM_003502.4	ENSP00000262320.3
AXIN1	ENST00000354866.7	c.878+14221G>T		intron_variant	Intron 2 of 9	1		ENSP00000346935.3
AXIN1	ENST00000461023.5	n.175+14221G>T		intron_variant	Intron 1 of 7	2
AXIN1	ENST00000481769.1	n.306-17244G>T		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27440 AN: 152020 Hom.: 2651 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.180 AC: 27455 AN: 152138 Hom.: 2655 Cov.: 33 AF XY: 0.182 AC XY: 13525 AN XY: 74390

African (AFR) AF: 0.179 AC: 7421 AN: 41464

American (AMR) AF: 0.144 AC: 2198 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 720 AN: 3462

East Asian (EAS) AF: 0.201 AC: 1041 AN: 5176

South Asian (SAS) AF: 0.277 AC: 1336 AN: 4818

European-Finnish (FIN) AF: 0.148 AC: 1569 AN: 10598

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12561 AN: 68016

Other (OTH) AF: 0.186 AC: 391 AN: 2106

Alfa AF: 0.186 Hom.: 3590

Bravo AF: 0.178

Asia WGS AF: 0.222 AC: 772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.6
DANN	Benign	0.56
PhyloP100		-0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs12921862; hg19: chr16-381927;