chr3-11583940-C-T

Position:

• chr3-11583940-C-T

Variant summary

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

The NM_001128219.3(VGLL4):​c.272+17893G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 152,126 control chromosomes in the GnomAD database, including 23,805 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 0.55 (23805 hom., cov: 33)
• Consequence: VGLL4 NM_001128219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113

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=-0.93).
• 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
VGLL4	NM_001128219.3	c.272+17893G>A		intron_variant		ENST00000430365.7	NP_001121691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VGLL4	ENST00000430365.7	c.272+17893G>A		intron_variant		2	NM_001128219.3	ENSP00000404251.2

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83731 AN: 152008 Hom.: 23779 Cov.: 33

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.551 AC: 83803 AN: 152126 Hom.: 23805 Cov.: 33 AF XY: 0.559 AC XY: 41585 AN XY: 74368

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.583

Alfa AF: 0.584 Hom.: 14870

Bravo AF: 0.538

Asia WGS AF: 0.707 AC: 2458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.26
DANN	Benign	0.55

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: rs6802119; hg19: chr3-11625414;