rs6726798

chr2-218436132-A-Cchr2-218436132-A-T

Variant summary

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

The NM_007127.3(VIL1):c.1827-350A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 152,178 control chromosomes in the GnomAD database, including 67,653 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 0.94 (67653 hom., cov: 32)
• Consequence: VIL1 NM_007127.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

Genes affected

VIL1 (HGNC:12690): (villin 1) This gene encodes a member of a family of calcium-regulated actin-binding proteins. This protein represents a dominant part of the brush border cytoskeleton which functions in the capping, severing, and bundling of actin filaments. Two mRNAs of 2.7 kb and 3.5 kb have been observed; they result from utilization of alternate poly-adenylation signals present in the terminal exon. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VIL1	NM_007127.3	c.1827-350A>C		intron_variant		ENST00000248444.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VIL1	ENST00000248444.10	c.1827-350A>C		intron_variant		1	NM_007127.3	P1
VIL1	ENST00000392114.6	c.894-350A>C		intron_variant		2
VIL1	ENST00000419986.1	c.534-350A>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.939 AC: 142732 AN: 152060 Hom.: 67628 Cov.: 32

Gnomad AFR AF: 0.790

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.973

Gnomad ASJ AF: 0.996

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.994

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.956

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

GnomAD4 genome AF: 0.938 AC: 142810 AN: 152178 Hom.: 67653 Cov.: 32 AF XY: 0.939 AC XY: 69831 AN XY: 74406

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.973

Gnomad4 ASJ AF: 0.996

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.994

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.957

Alfa AF: 0.986 Hom.: 58796

Bravo AF: 0.931

Asia WGS AF: 0.982 AC: 3413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	1.3
Dann	Benign	0.74

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: rs6726798; hg19: chr2-219300855;