3-11583940-C-T

Variant names:

• chr3-11583940-C-T
• rs6802119
• NM_001128219.3:c.272+17893G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.684 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VGLL4	NM_001128219.3	MANE Select	c.272+17893G>A		intron	N/A	NP_001121691.1
	VGLL4	NM_001284390.2		c.269+17893G>A		intron	N/A	NP_001271319.1
	VGLL4	NM_014667.4		c.254+17893G>A		intron	N/A	NP_055482.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VGLL4	ENST00000430365.7	TSL:2 MANE Select	c.272+17893G>A		intron	N/A	ENSP00000404251.2
	VGLL4	ENST00000426568.5	TSL:1	c.269+17893G>A		intron	N/A	ENSP00000413030.2
	VGLL4	ENST00000273038.7	TSL:1	c.254+17893G>A		intron	N/A	ENSP00000273038.3

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

African (AFR) AF: 0.415 AC: 17232 AN: 41504

American (AMR) AF: 0.603 AC: 9218 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2091 AN: 3468

East Asian (EAS) AF: 0.615 AC: 3175 AN: 5162

South Asian (SAS) AF: 0.703 AC: 3393 AN: 4824

European-Finnish (FIN) AF: 0.675 AC: 7135 AN: 10578

Middle Eastern (MID) AF: 0.575 AC: 168 AN: 292

European-Non Finnish (NFE) AF: 0.583 AC: 39643 AN: 67988

Other (OTH) AF: 0.583 AC: 1228 AN: 2108

Alfa AF: 0.564 Hom.: 21668

Bravo AF: 0.538

Asia WGS AF: 0.707 AC: 2458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.26
DANN	Benign	0.55
PhyloP100		-0.11
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: rs6802119; hg19: chr3-11625414;