2-218428603-C-T

Position:

• chr2-218428603-C-T

Variant summary

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

The NM_007127.3(VIL1):​c.567+266C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,064 control chromosomes in the GnomAD database, including 19,430 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 0.46 (19430 hom., cov: 32)
• Consequence: VIL1 NM_007127.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIL1	NM_007127.3	c.567+266C>T		intron_variant		ENST00000248444.10	NP_009058.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIL1	ENST00000248444.10	c.567+266C>T		intron_variant		1	NM_007127.3	ENSP00000248444.5
VIL1	ENST00000440053.1	c.567+266C>T		intron_variant		1		ENSP00000409270.1
VIL1	ENST00000392114.6	c.-183-865C>T		intron_variant		2		ENSP00000375962.2

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70378 AN: 151948 Hom.: 19430 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.463 AC: 70370 AN: 152064 Hom.: 19430 Cov.: 32 AF XY: 0.470 AC XY: 34968 AN XY: 74324

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.766

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.518

Alfa AF: 0.543 Hom.: 17793

Bravo AF: 0.444

Asia WGS AF: 0.680 AC: 2362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.37
DANN	Benign	0.50

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: rs4674305; hg19: chr2-219293326;