chr12-48979249-C-G

Position:

• chr12-48979249-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005430.4(WNT1):​c.105-219C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00671 in 152,360 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0067 (8 hom., cov: 33)
• Consequence: WNT1 NM_005430.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.129

Genes affected

WNT1 (HGNC:12774): (Wnt family member 1) The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It is very conserved in evolution, and the protein encoded by this gene is known to be 98% identical to the mouse Wnt1 protein at the amino acid level. The studies in mouse indicate that the Wnt1 protein functions in the induction of the mesencephalon and cerebellum. This gene was originally considered as a candidate gene for Joubert syndrome, an autosomal recessive disorder with cerebellar hypoplasia as a leading feature. However, further studies suggested that the gene mutations might not have a significant role in Joubert syndrome. This gene is clustered with another family member, WNT10B, in the chromosome 12q13 region. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-48979249-C-G is Benign according to our data. Variant chr12-48979249-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1219896.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00671 (1023/152360) while in subpopulation NFE AF= 0.00988 (672/68030). AF 95% confidence interval is 0.00926. There are 8 homozygotes in gnomad4. There are 480 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT1	NM_005430.4	c.105-219C>G		intron_variant		ENST00000293549.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT1	ENST00000293549.4	c.105-219C>G		intron_variant		1	NM_005430.4	P1

Frequencies

GnomAD3 genomes AF: 0.00672 AC: 1023 AN: 152242 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.00706

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00998

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00988

Gnomad OTH AF: 0.00669

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

GnomAD4 genome AF: 0.00671 AC: 1023 AN: 152360 Hom.: 8 Cov.: 33 AF XY: 0.00644 AC XY: 480 AN XY: 74500

Gnomad4 AFR AF: 0.00151

Gnomad4 AMR AF: 0.00705

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00998

Gnomad4 NFE AF: 0.00988

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00810 Hom.: 0

Bravo AF: 0.00665

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.4
DANN	Benign	0.59

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: rs78196399; hg19: chr12-49373032;