rs214250

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-298222-C-A
• chr16-298222-C-G
• chr16-298222-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003502.4(AXIN1):​c.1284G>T​(p.Ser428Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AXIN1 NM_003502.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=0.12 with no splicing effect.

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>T	p.Ser428Ser	synonymous	Exon 6 of 11	NP_003493.1
	AXIN1	NM_181050.3		c.1284G>T	p.Ser428Ser	synonymous	Exon 6 of 10	NP_851393.1
	AXIN1	NR_134879.2		n.1623G>T		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>T	p.Ser428Ser	synonymous	Exon 6 of 11	ENSP00000262320.3
	AXIN1	ENST00000354866.7	TSL:1	c.1284G>T	p.Ser428Ser	synonymous	Exon 6 of 10	ENSP00000346935.3
	AXIN1	ENST00000957925.1		c.1299G>T	p.Ser433Ser	synonymous	Exon 6 of 11	ENSP00000627984.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1387876 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 685096

African (AFR) AF: 0.00 AC: 0 AN: 31606

American (AMR) AF: 0.00 AC: 0 AN: 35784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 35772

South Asian (SAS) AF: 0.00 AC: 0 AN: 79276

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079104

Other (OTH) AF: 0.00 AC: 0 AN: 57950

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.38
DANN	Benign	0.34
PhyloP100		0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;