3-11582737-C-A

Position:

• chr3-11582737-C-A

Variant summary

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

The NM_001128219.3(VGLL4):​c.273-17718G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 152,222 control chromosomes in the GnomAD database, including 57,424 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 0.87 (57424 hom., cov: 33)
• Consequence: VGLL4 NM_001128219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103

Genes affected

VGLL4 (HGNC:28966): (vestigial like family member 4) Predicted to enable transcription coactivator binding activity. Involved in negative regulation of Wnt signaling pathway; negative regulation of cell growth; and negative regulation of hippo signaling. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VGLL4	NM_001128219.3	c.273-17718G>T		intron_variant		ENST00000430365.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VGLL4	ENST00000430365.7	c.273-17718G>T		intron_variant		2	NM_001128219.3	P1

Frequencies

GnomAD3 genomes AF: 0.867 AC: 131931 AN: 152104 Hom.: 57404 Cov.: 33

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.974

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.898

Gnomad OTH AF: 0.894

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

GnomAD4 genome AF: 0.867 AC: 132004 AN: 152222 Hom.: 57424 Cov.: 33 AF XY: 0.866 AC XY: 64442 AN XY: 74416

Gnomad4 AFR AF: 0.806

Gnomad4 AMR AF: 0.851

Gnomad4 ASJ AF: 0.931

Gnomad4 EAS AF: 0.965

Gnomad4 SAS AF: 0.860

Gnomad4 FIN AF: 0.850

Gnomad4 NFE AF: 0.898

Gnomad4 OTH AF: 0.895

Alfa AF: 0.884 Hom.: 37354

Bravo AF: 0.867

Asia WGS AF: 0.878 AC: 3050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.5
DANN	Benign	0.64

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: rs892932; hg19: chr3-11624211;