chr16-323817-C-A

Variant names:

• chr16-323817-C-A
• rs11646942
• NM_003502.4:c.879-9134G>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.879-9134G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,402 control chromosomes in the GnomAD database, including 6,006 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 0.28 (6006 hom., cov: 32)
• Consequence: AXIN1 NM_003502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.386 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.879-9134G>T		intron	N/A	NP_003493.1	A0A0S2Z4R0
	AXIN1	NM_181050.3		c.879-9134G>T		intron	N/A	NP_851393.1	O15169-2
	AXIN1	NR_134879.2		n.1315-9134G>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.879-9134G>T		intron	N/A	ENSP00000262320.3	O15169-1
	AXIN1	ENST00000354866.7	TSL:1	c.879-9134G>T		intron	N/A	ENSP00000346935.3	O15169-2
	AXIN1	ENST00000957925.1		c.879-9134G>T		intron	N/A	ENSP00000627984.1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41750 AN: 151284 Hom.: 6001 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.276 AC: 41786 AN: 151402 Hom.: 6006 Cov.: 32 AF XY: 0.281 AC XY: 20815 AN XY: 73972

African (AFR) AF: 0.270 AC: 11093 AN: 41064

American (AMR) AF: 0.282 AC: 4296 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 709 AN: 3466

East Asian (EAS) AF: 0.151 AC: 777 AN: 5158

South Asian (SAS) AF: 0.401 AC: 1929 AN: 4808

European-Finnish (FIN) AF: 0.339 AC: 3559 AN: 10490

Middle Eastern (MID) AF: 0.207 AC: 60 AN: 290

European-Non Finnish (NFE) AF: 0.276 AC: 18741 AN: 67884

Other (OTH) AF: 0.245 AC: 517 AN: 2108

Alfa AF: 0.266 Hom.: 6762

Bravo AF: 0.262

Asia WGS AF: 0.295 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.86
DANN	Benign	0.50
PhyloP100		-0.75
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: rs11646942; hg19: chr16-373817;