3-11634315-T-C

Position:

• chr3-11634315-T-C

Variant summary

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

The NM_001128219.3(VGLL4):​c.82+9122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,896 control chromosomes in the GnomAD database, including 5,242 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 0.25 (5242 hom., cov: 31)
• Consequence: VGLL4 NM_001128219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VGLL4	NM_001128219.3	c.82+9122A>G		intron_variant		ENST00000430365.7	NP_001121691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VGLL4	ENST00000430365.7	c.82+9122A>G		intron_variant		2	NM_001128219.3	ENSP00000404251	P1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38407 AN: 151776 Hom.: 5227 Cov.: 31

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.253 AC: 38477 AN: 151896 Hom.: 5242 Cov.: 31 AF XY: 0.261 AC XY: 19376 AN XY: 74218

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.276

Alfa AF: 0.243 Hom.: 7318

Bravo AF: 0.258

Asia WGS AF: 0.422 AC: 1463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.40

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: rs6782029; hg19: chr3-11675789;