rs11648673

Positions:

• chr16-327794-G-A
• chr16-327794-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003502.4(AXIN1):​c.879-13111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,202 control chromosomes in the GnomAD database, including 6,014 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 0.27 (6014 hom., cov: 33)
• Consequence: AXIN1 NM_003502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.833

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AXIN1	NM_003502.4	c.879-13111C>T		intron_variant		ENST00000262320.8	NP_003493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AXIN1	ENST00000262320.8	c.879-13111C>T		intron_variant		1	NM_003502.4	ENSP00000262320.3
AXIN1	ENST00000354866.7	c.879-13111C>T		intron_variant		1		ENSP00000346935.3
AXIN1	ENST00000461023.5	n.176-13111C>T		intron_variant		2
AXIN1	ENST00000481769.1	n.306-13111C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41759 AN: 152084 Hom.: 6009 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.275 AC: 41794 AN: 152202 Hom.: 6014 Cov.: 33 AF XY: 0.280 AC XY: 20826 AN XY: 74404

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.244

Alfa AF: 0.273 Hom.: 10529

Bravo AF: 0.261

Asia WGS AF: 0.298 AC: 1034 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs11648673; hg19: chr16-377794;