16-298222-C-T

Variant names:

• chr16-298222-C-T
• rs214250
• NM_003502.4:c.1284G>A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003502.4(AXIN1):​c.1284G>A​(p.Ser428Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,540,012 control chromosomes in the GnomAD database, including 39,359 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 0.25 (5559 hom., cov: 33)
  • Exomes 𝑓: 0.21 (33800 hom.)
• Consequence: AXIN1 NM_003502.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=0.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXIN1	NM_003502.4	c.1284G>A	p.Ser428Ser	synonymous_variant	Exon 6 of 11	ENST00000262320.8	NP_003493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXIN1	ENST00000262320.8	c.1284G>A	p.Ser428Ser	synonymous_variant	Exon 6 of 11	1	NM_003502.4	ENSP00000262320.3
AXIN1	ENST00000354866.7	c.1284G>A	p.Ser428Ser	synonymous_variant	Exon 6 of 10	1		ENSP00000346935.3
AXIN1	ENST00000461023.5	n.581G>A		non_coding_transcript_exon_variant	Exon 5 of 8	2
AXIN1	ENST00000481769.1	n.711G>A		non_coding_transcript_exon_variant	Exon 5 of 5	3

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38286 AN: 152050 Hom.: 5548 Cov.: 33

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0578

Gnomad SAS AF: 0.0938

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.227

GnomAD3 exomes AF: 0.176 AC: 25077 AN: 142552 Hom.: 2845 AF XY: 0.171 AC XY: 13163 AN XY: 76976

Gnomad AFR exome AF: 0.413

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.199

Gnomad EAS exome AF: 0.0536

Gnomad SAS exome AF: 0.0953

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.224

Gnomad OTH exome AF: 0.191

GnomAD4 exome AF: 0.213 AC: 295527 AN: 1387844 Hom.: 33800 Cov.: 38 AF XY: 0.210 AC XY: 143748 AN XY: 685084

Gnomad4 AFR exome AF: 0.406

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.195

Gnomad4 EAS exome AF: 0.0744

Gnomad4 SAS exome AF: 0.0977

Gnomad4 FIN exome AF: 0.211

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.252 AC: 38336 AN: 152168 Hom.: 5559 Cov.: 33 AF XY: 0.245 AC XY: 18226 AN XY: 74386

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.0577

Gnomad4 SAS AF: 0.0945

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.224

Alfa AF: 0.221 Hom.: 4098

Bravo AF: 0.259

Asia WGS AF: 0.0940 AC: 328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.6
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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: rs214250; hg19: chr16-348222; COSMIC: COSV51984059; COSMIC: COSV51984059;