16-298687-T-G

Position:

• chr16-298687-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AXIN1	NM_003502.4	c.1255-436A>C		intron_variant		ENST00000262320.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AXIN1	ENST00000262320.8	c.1255-436A>C		intron_variant		1	NM_003502.4	A1
AXIN1	ENST00000354866.7	c.1255-436A>C		intron_variant		1		P4
AXIN1	ENST00000461023.5	n.552-436A>C		intron_variant, non_coding_transcript_variant		2
AXIN1	ENST00000481769.1	n.682-436A>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.356

Alfa AF: 0.378 Hom.: 14488

Bravo AF: 0.372

Asia WGS AF: 0.274 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.49

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: rs214249; hg19: chr16-348687; COSMIC: COSV51985027;