rs214246

chr16-299293-A-G

Variant summary

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

The NM_003502.4(AXIN1):c.1255-1042T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 951,116 control chromosomes in the GnomAD database, including 124,186 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 0.57 (26922 hom., cov: 34)
  • Exomes 𝑓: 0.49 (97264 hom.)
• Consequence: AXIN1 NM_003502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416

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=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AXIN1	NM_003502.4	c.1255-1042T>C		intron_variant		ENST00000262320.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AXIN1	ENST00000262320.8	c.1255-1042T>C		intron_variant		1	NM_003502.4	A1
AXIN1	ENST00000354866.7	c.1255-1042T>C		intron_variant		1		P4
AXIN1	ENST00000461023.5	n.552-1042T>C		intron_variant, non_coding_transcript_variant		2
AXIN1	ENST00000481769.1	n.682-1042T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85960 AN: 152078 Hom.: 26867 Cov.: 34

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.520

GnomAD4 exome AF: 0.490 AC: 391172 AN: 798920 Hom.: 97264 AF XY: 0.490 AC XY: 181347 AN XY: 369928

Gnomad4 AFR exome AF: 0.884

Gnomad4 AMR exome AF: 0.328

Gnomad4 ASJ exome AF: 0.451

Gnomad4 EAS exome AF: 0.321

Gnomad4 SAS exome AF: 0.580

Gnomad4 FIN exome AF: 0.388

Gnomad4 NFE exome AF: 0.481

Gnomad4 OTH exome AF: 0.493

GnomAD4 genome AF: 0.566 AC: 86070 AN: 152196 Hom.: 26922 Cov.: 34 AF XY: 0.560 AC XY: 41655 AN XY: 74402

Gnomad4 AFR AF: 0.844

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.524

Alfa AF: 0.485 Hom.: 24722

Bravo AF: 0.570

Asia WGS AF: 0.542 AC: 1882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	1.2
Dann	Benign	0.50

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: rs214246; hg19: chr16-349293; COSMIC: COSV51985050;