rs1981492

Positions:

• chr16-306689-G-A
• chr16-306689-G-T

Variant summary

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

The NM_003502.4(AXIN1):​c.1117-2248C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,154 control chromosomes in the GnomAD database, including 14,796 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 0.44 (14796 hom., cov: 33)
• Consequence: AXIN1 NM_003502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AXIN1	NM_003502.4	c.1117-2248C>T		intron_variant		ENST00000262320.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AXIN1	ENST00000262320.8	c.1117-2248C>T		intron_variant		1	NM_003502.4	A1
AXIN1	ENST00000354866.7	c.1117-2248C>T		intron_variant		1		P4
AXIN1	ENST00000461023.5	n.414-2248C>T		intron_variant, non_coding_transcript_variant		2
AXIN1	ENST00000481769.1	n.544-2248C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66335 AN: 152036 Hom.: 14785 Cov.: 33

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.401

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.436 AC: 66388 AN: 152154 Hom.: 14796 Cov.: 33 AF XY: 0.441 AC XY: 32782 AN XY: 74400

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.407

Alfa AF: 0.460 Hom.: 8830

Bravo AF: 0.418

Asia WGS AF: 0.473 AC: 1641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.77

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: rs1981492; hg19: chr16-356689;