NM_007127.3:c.567+266C>T

Variant names:

• chr2-218428603-C-T
• rs4674305
• NM_007127.3:c.567+266C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007127.3. 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
	VIL1	NM_007127.3	MANE Select	c.567+266C>T		intron	N/A	NP_009058.2	P09327-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VIL1	ENST00000248444.10	TSL:1 MANE Select	c.567+266C>T		intron	N/A	ENSP00000248444.5	P09327-1
	VIL1	ENST00000440053.1	TSL:1	c.567+266C>T		intron	N/A	ENSP00000409270.1	P09327-2
	VIL1	ENST00000879964.1		c.567+266C>T		intron	N/A	ENSP00000550023.1

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

African (AFR) AF: 0.144 AC: 5975 AN: 41476

American (AMR) AF: 0.552 AC: 8442 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2033 AN: 3468

East Asian (EAS) AF: 0.766 AC: 3960 AN: 5168

South Asian (SAS) AF: 0.664 AC: 3201 AN: 4822

European-Finnish (FIN) AF: 0.576 AC: 6067 AN: 10540

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38846 AN: 67988

Other (OTH) AF: 0.518 AC: 1095 AN: 2112

Alfa AF: 0.528 Hom.: 22031

Bravo AF: 0.444

Asia WGS AF: 0.680 AC: 2362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.37
DANN	Benign	0.50
PhyloP100		-0.42
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: rs4674305; hg19: chr2-219293326;