14-100128941-T-A

Position:

• chr14-100128941-T-A

Variant summary

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

The NM_016337.3(EVL):​c.717+193T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 152,188 control chromosomes in the GnomAD database, including 49,692 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 0.81 (49692 hom., cov: 33)
• Consequence: EVL NM_016337.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

Genes affected

EVL (HGNC:20234): (Enah/Vasp-like) Predicted to enable SH3 domain binding activity and profilin binding activity. Involved in negative regulation of epithelial cell migration; negative regulation of ruffle assembly; and positive regulation of stress fiber assembly. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVL	NM_016337.3	c.717+193T>A		intron_variant		ENST00000392920.8	NP_057421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVL	ENST00000392920.8	c.717+193T>A		intron_variant		1	NM_016337.3	ENSP00000376652	P1

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122455 AN: 152070 Hom.: 49641 Cov.: 33

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.765

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

GnomAD4 genome AF: 0.805 AC: 122565 AN: 152188 Hom.: 49692 Cov.: 33 AF XY: 0.810 AC XY: 60268 AN XY: 74394

Gnomad4 AFR AF: 0.904

Gnomad4 AMR AF: 0.797

Gnomad4 ASJ AF: 0.722

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.750

Gnomad4 OTH AF: 0.765

Alfa AF: 0.723 Hom.: 2162

Bravo AF: 0.806

Asia WGS AF: 0.822 AC: 2860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.45
DANN	Benign	0.53

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: rs3783337; hg19: chr14-100595278; COSMIC: COSV67374965; COSMIC: COSV67374965;