rs12374138

Variant names:

• chr3-11657322-G-A
• rs12374138
• ENST00000426568.5:c.79+13940C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.9).
• 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 rank	MANE	Protein	UniProt
VGLL4	NM_001284390.2	c.79+13940C>T		intron_variant	Intron 3 of 6		NP_001271319.1
VGLL4	NM_014667.4	c.64+45649C>T		intron_variant	Intron 2 of 5		NP_055482.2
VGLL4	XM_047449259.1	c.91+45649C>T		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+45649C>T		intron_variant	Intron 5 of 5	5		ENSP00000485472.1

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

African (AFR) AF: 0.178 AC: 7374 AN: 41484

American (AMR) AF: 0.341 AC: 5212 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1221 AN: 3466

East Asian (EAS) AF: 0.365 AC: 1882 AN: 5160

South Asian (SAS) AF: 0.232 AC: 1114 AN: 4812

European-Finnish (FIN) AF: 0.419 AC: 4410 AN: 10520

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29536 AN: 67984

Other (OTH) AF: 0.344 AC: 728 AN: 2114

Alfa AF: 0.377 Hom.: 9742

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
PhyloP100		-0.34
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: rs12374138; hg19: chr3-11698796;