rs7359414

Positions:

• chr16-312638-T-G

Variant summary

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

The NM_003502.4(AXIN1):​c.1019+1905A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 152,072 control chromosomes in the GnomAD database, including 22,481 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 0.54 (22481 hom., cov: 33)
• Consequence: AXIN1 NM_003502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AXIN1	NM_003502.4	c.1019+1905A>C		intron_variant		ENST00000262320.8	NP_003493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AXIN1	ENST00000262320.8	c.1019+1905A>C		intron_variant		1	NM_003502.4	ENSP00000262320.3
AXIN1	ENST00000354866.7	c.1019+1905A>C		intron_variant		1		ENSP00000346935.3
AXIN1	ENST00000461023.5	n.316+1905A>C		intron_variant		2
AXIN1	ENST00000481769.1	n.446+1905A>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81448 AN: 151954 Hom.: 22450 Cov.: 33

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.536 AC: 81532 AN: 152072 Hom.: 22481 Cov.: 33 AF XY: 0.538 AC XY: 40006 AN XY: 74334

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.514

Alfa AF: 0.503 Hom.: 25613

Bravo AF: 0.529

Asia WGS AF: 0.538 AC: 1869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.45

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: rs7359414; hg19: chr16-362638;