chr3-11582737-C-A

Variant names:

• chr3-11582737-C-A
• rs892932
• NM_001128219.3:c.273-17718G>T

Variant summary

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

The NM_001128219.3(VGLL4):​c.273-17718G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 152,222 control chromosomes in the GnomAD database, including 57,424 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 0.87 (57424 hom., cov: 33)
• Consequence: VGLL4 NM_001128219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103
• Publications: 2 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128219.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VGLL4	NM_001128219.3	MANE Select	c.273-17718G>T		intron	N/A	NP_001121691.1	Q14135-4
	VGLL4	NM_001284390.2		c.270-17718G>T		intron	N/A	NP_001271319.1	A0A0A6YYI5
	VGLL4	NM_014667.4		c.255-17718G>T		intron	N/A	NP_055482.2	Q14135-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VGLL4	ENST00000430365.7	TSL:2 MANE Select	c.273-17718G>T		intron	N/A	ENSP00000404251.2	Q14135-4
	VGLL4	ENST00000426568.5	TSL:1	c.270-17718G>T		intron	N/A	ENSP00000413030.2	A0A0A6YYI5
	VGLL4	ENST00000273038.7	TSL:1	c.255-17718G>T		intron	N/A	ENSP00000273038.3	Q14135-1

Frequencies

GnomAD3 genomes AF: 0.867 AC: 131931 AN: 152104 Hom.: 57404 Cov.: 33

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.974

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.898

Gnomad OTH AF: 0.894

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

GnomAD4 genome AF: 0.867 AC: 132004 AN: 152222 Hom.: 57424 Cov.: 33 AF XY: 0.866 AC XY: 64442 AN XY: 74416

African (AFR) AF: 0.806 AC: 33453 AN: 41510

American (AMR) AF: 0.851 AC: 13025 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.931 AC: 3234 AN: 3472

East Asian (EAS) AF: 0.965 AC: 4986 AN: 5166

South Asian (SAS) AF: 0.860 AC: 4141 AN: 4816

European-Finnish (FIN) AF: 0.850 AC: 9019 AN: 10608

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.898 AC: 61099 AN: 68028

Other (OTH) AF: 0.895 AC: 1893 AN: 2114

Alfa AF: 0.889 Hom.: 121630

Bravo AF: 0.867

Asia WGS AF: 0.878 AC: 3050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.5
DANN	Benign	0.64
PhyloP100		-0.10
PromoterAI		0.0039	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs892932; hg19: chr3-11624211;