rs12374138

Positions:

• chr3-11657322-G-A
• chr3-11657322-G-C
• chr3-11657322-G-T

Variant summary

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

The ENST00000426568.5(VGLL4):​c.79+13940C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,006 control chromosomes in the GnomAD database, including 9,854 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 0.34 (9854 hom., cov: 32)
• Consequence: VGLL4 ENST00000426568.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VGLL4	NM_001284390.2	c.79+13940C>T		intron_variant			NP_001271319.1
VGLL4	NM_014667.4	c.64+45649C>T		intron_variant			NP_055482.2
VGLL4	XM_024453835.2	c.64+45649C>T		intron_variant			XP_024309603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VGLL4	ENST00000273038.7	c.64+45649C>T		intron_variant		1		ENSP00000273038
VGLL4	ENST00000426568.5	c.79+13940C>T		intron_variant		1		ENSP00000413030
VGLL4	ENST00000417206.6	c.64+45649C>T		intron_variant		4		ENSP00000391932

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51912 AN: 151888 Hom.: 9857 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.342 AC: 51920 AN: 152006 Hom.: 9854 Cov.: 32 AF XY: 0.339 AC XY: 25179 AN XY: 74268

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.344

Alfa AF: 0.375 Hom.: 8155

Bravo AF: 0.326

Asia WGS AF: 0.284 AC: 989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12374138; hg19: chr3-11698796;