Genetic Variant EVL:c.965-516C>A (chr14-100137062-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016337.3(EVL):c.965-516C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 159,166 control chromosomes in the GnomAD database, including 51,042 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 0.80 ( 49404 hom., cov: 33)

Exomes 𝑓: 0.67 ( 1638 hom. )

Consequence

EVL
NM_016337.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.907

Publications

6 publications found

Variant links:

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]

EVL links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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 link	c.965-516C>A		intron_variant	Intron 9 of 13	ENST00000392920.8	NP_057421.1	Q9UI08-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVL	ENST00000392920.8 link	c.965-516C>A		intron_variant	Intron 9 of 13	1	NM_016337.3	ENSP00000376652.3		Q9UI08-2

Frequencies

GnomAD3 genomes

AF:

0.803

AC:

122064

AN:

152052

Hom.:

49353

Cov.:

show subpopulations

Gnomad AFR

AF:

0.903

Gnomad AMI

AF:

0.833

Gnomad AMR

AF:

0.795

Gnomad ASJ

AF:

0.727

Gnomad EAS

AF:

0.820

Gnomad SAS

AF:

0.765

Gnomad FIN

AF:

0.809

Gnomad MID

AF:

0.690

Gnomad NFE

AF:

0.749

Gnomad OTH

AF:

0.767

GnomAD4 exome

AF:

0.674

AC:

4712

AN:

6996

Hom.:

1638

Cov.:

AF XY:

0.672

AC XY:

2450

AN XY:

3648

show subpopulations

African (AFR)

AF:

0.764

AC:

AN:

106

American (AMR)

AF:

0.749

AC:

1330

AN:

1776

Ashkenazi Jewish (ASJ)

AF:

0.613

AC:

AN:

East Asian (EAS)

AF:

0.680

AC:

283

AN:

416

South Asian (SAS)

AF:

0.625

AC:

440

AN:

704

European-Finnish (FIN)

AF:

0.417

AC:

AN:

Middle Eastern (MID)

AF:

0.333

AC:

AN:

European-Non Finnish (NFE)

AF:

0.647

AC:

2341

AN:

3618

Other (OTH)

AF:

0.677

AC:

180

AN:

266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

126

190

253

316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.803

AC:

122174

AN:

152170

Hom.:

49404

Cov.:

AF XY:

0.807

AC XY:

60003

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.903

AC:

37509

AN:

41530

American (AMR)

AF:

0.795

AC:

12168

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.727

AC:

2524

AN:

3472

East Asian (EAS)

AF:

0.820

AC:

4232

AN:

5158

South Asian (SAS)

AF:

0.764

AC:

3680

AN:

4818

European-Finnish (FIN)

AF:

0.809

AC:

8562

AN:

10584

Middle Eastern (MID)

AF:

0.684

AC:

201

AN:

294

European-Non Finnish (NFE)

AF:

0.749

AC:

50931

AN:

68006

Other (OTH)

AF:

0.766

AC:

1609

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1237

2473

3710

4946

6183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

872

1744

2616

3488

4360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.762

Hom.:

124897

Bravo

AF:

0.805

Asia WGS

AF:

0.818

AC:

2843

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.14

(source)

DANN

Benign

0.44

PhyloP100

-0.91

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over