chr3-11652993-T-C

Variant names:

• chr3-11652993-T-C
• rs4684792
• ENST00000426568.5:c.79+18269A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000426568.5(VGLL4):​c.79+18269A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,084 control chromosomes in the GnomAD database, including 42,847 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 0.75 (42847 hom., cov: 32)
• Consequence: VGLL4 ENST00000426568.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.854
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VGLL4	NM_001284390.2	c.79+18269A>G		intron_variant	Intron 3 of 6		NP_001271319.1
VGLL4	NM_014667.4	c.64+49978A>G		intron_variant	Intron 2 of 5		NP_055482.2
VGLL4	XM_047449259.1	c.91+49978A>G		intron_variant	Intron 2 of 5		XP_047305215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VGLL4	ENST00000623028.1	c.64+49978A>G		intron_variant	Intron 5 of 5	5		ENSP00000485472.1

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113878 AN: 151966 Hom.: 42801 Cov.: 32

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.755

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

GnomAD4 genome AF: 0.749 AC: 113980 AN: 152084 Hom.: 42847 Cov.: 32 AF XY: 0.749 AC XY: 55689 AN XY: 74326

African (AFR) AF: 0.798 AC: 33096 AN: 41486

American (AMR) AF: 0.783 AC: 11983 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2381 AN: 3470

East Asian (EAS) AF: 0.630 AC: 3257 AN: 5170

South Asian (SAS) AF: 0.655 AC: 3149 AN: 4810

European-Finnish (FIN) AF: 0.714 AC: 7527 AN: 10538

Middle Eastern (MID) AF: 0.771 AC: 225 AN: 292

European-Non Finnish (NFE) AF: 0.737 AC: 50106 AN: 67992

Other (OTH) AF: 0.752 AC: 1592 AN: 2116

Alfa AF: 0.741 Hom.: 91227

Bravo AF: 0.756

Asia WGS AF: 0.678 AC: 2359 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	1.1
DANN	Benign	0.62
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4684792; hg19: chr3-11694467;