NM_003502.4:c.1284G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 28 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 -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.

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.1284G>A	p.Ser428Ser	synonymous	Exon 6 of 11	NP_003493.1
	AXIN1	NM_181050.3		c.1284G>A	p.Ser428Ser	synonymous	Exon 6 of 10	NP_851393.1
	AXIN1	NR_134879.2		n.1623G>A		non_coding_transcript_exon	Exon 5 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXIN1	ENST00000262320.8	TSL:1 MANE Select	c.1284G>A	p.Ser428Ser	synonymous	Exon 6 of 11	ENSP00000262320.3
	AXIN1	ENST00000354866.7	TSL:1	c.1284G>A	p.Ser428Ser	synonymous	Exon 6 of 10	ENSP00000346935.3
	AXIN1	ENST00000957925.1		c.1299G>A	p.Ser433Ser	synonymous	Exon 6 of 11	ENSP00000627984.1

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

GnomAD2 exomes AF: 0.176 AC: 25077 AN: 142552 AF XY: 0.171

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 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

African (AFR) AF: 0.406 AC: 12839 AN: 31606

American (AMR) AF: 0.112 AC: 3996 AN: 35784

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 4909 AN: 25176

East Asian (EAS) AF: 0.0744 AC: 2663 AN: 35772

South Asian (SAS) AF: 0.0977 AC: 7744 AN: 79276

European-Finnish (FIN) AF: 0.211 AC: 7912 AN: 37484

Middle Eastern (MID) AF: 0.212 AC: 1208 AN: 5698

European-Non Finnish (NFE) AF: 0.225 AC: 242400 AN: 1079098

Other (OTH) AF: 0.205 AC: 11856 AN: 57950

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

African (AFR) AF: 0.394 AC: 16356 AN: 41500

American (AMR) AF: 0.155 AC: 2378 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 668 AN: 3468

East Asian (EAS) AF: 0.0577 AC: 298 AN: 5162

South Asian (SAS) AF: 0.0945 AC: 456 AN: 4826

European-Finnish (FIN) AF: 0.197 AC: 2091 AN: 10604

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15174 AN: 67992

Other (OTH) AF: 0.224 AC: 473 AN: 2110

Alfa AF: 0.228 Hom.: 5628

Bravo AF: 0.259

Asia WGS AF: 0.0940 AC: 328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.6
DANN	Benign	0.65
PhyloP100		0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
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: rs214250; hg19: chr16-348222; COSMIC: COSV51984059; COSMIC: COSV51984059;