14-100115299-T-C

Variant names:

• chr14-100115299-T-C
• rs11160570
• NM_016337.3:c.359-8240T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016337.3(EVL):​c.359-8240T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,172 control chromosomes in the GnomAD database, including 49,729 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 (49729 hom., cov: 32)
• Consequence: EVL NM_016337.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.544
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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 rank	MANE	Protein	UniProt
EVL	NM_016337.3	c.359-8240T>C		intron_variant	Intron 3 of 13	ENST00000392920.8	NP_057421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVL	ENST00000392920.8	c.359-8240T>C		intron_variant	Intron 3 of 13	1	NM_016337.3	ENSP00000376652.3

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122493 AN: 152054 Hom.: 49679 Cov.: 32

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.768

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

GnomAD4 genome AF: 0.806 AC: 122601 AN: 152172 Hom.: 49729 Cov.: 32 AF XY: 0.810 AC XY: 60275 AN XY: 74372

African (AFR) AF: 0.904 AC: 37543 AN: 41540

American (AMR) AF: 0.797 AC: 12198 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2504 AN: 3472

East Asian (EAS) AF: 0.825 AC: 4255 AN: 5160

South Asian (SAS) AF: 0.771 AC: 3720 AN: 4824

European-Finnish (FIN) AF: 0.829 AC: 8770 AN: 10584

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.751 AC: 51035 AN: 67986

Other (OTH) AF: 0.767 AC: 1617 AN: 2108

Alfa AF: 0.792 Hom.: 6210

Bravo AF: 0.806

Asia WGS AF: 0.827 AC: 2875 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.77
PhyloP100		-0.54
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: rs11160570; hg19: chr14-100581636;