chr16-298687-T-G

Variant names:

• chr16-298687-T-G
• rs214249
• NM_003502.4:c.1255-436A>C

Variant summary

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

The NM_003502.4(AXIN1):​c.1255-436A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,850 control chromosomes in the GnomAD database, including 10,911 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 0.37 (10911 hom., cov: 31)
• Consequence: AXIN1 NM_003502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• Publications: 13 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 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.1255-436A>C		intron	N/A	NP_003493.1	A0A0S2Z4R0
	AXIN1	NM_181050.3		c.1255-436A>C		intron	N/A	NP_851393.1	O15169-2
	AXIN1	NR_134879.2		n.1594-436A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXIN1	ENST00000262320.8	TSL:1 MANE Select	c.1255-436A>C		intron	N/A	ENSP00000262320.3	O15169-1
	AXIN1	ENST00000354866.7	TSL:1	c.1255-436A>C		intron	N/A	ENSP00000346935.3	O15169-2
	AXIN1	ENST00000957925.1		c.1270-436A>C		intron	N/A	ENSP00000627984.1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56653 AN: 151730 Hom.: 10899 Cov.: 31

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.373 AC: 56706 AN: 151850 Hom.: 10911 Cov.: 31 AF XY: 0.367 AC XY: 27229 AN XY: 74180

African (AFR) AF: 0.427 AC: 17686 AN: 41380

American (AMR) AF: 0.264 AC: 4037 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1175 AN: 3468

East Asian (EAS) AF: 0.183 AC: 945 AN: 5160

South Asian (SAS) AF: 0.307 AC: 1478 AN: 4814

European-Finnish (FIN) AF: 0.328 AC: 3458 AN: 10528

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26564 AN: 67918

Other (OTH) AF: 0.356 AC: 752 AN: 2112

Alfa AF: 0.379 Hom.: 26198

Bravo AF: 0.372

Asia WGS AF: 0.274 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.49
PhyloP100		-0.0060
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: rs214249; hg19: chr16-348687; COSMIC: COSV51985027;