dbSNP rs939779373: EVC:p.Gly5Glu (chr4-5711394-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153717.3(EVC):c.14G>A(p.Gly5Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G5V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EVC
NM_153717.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.49

Publications

0 publications found

Variant links:

Genes affected

EVC (HGNC:3497): (EvC ciliary complex subunit 1) This gene encodes a protein containing a leucine zipper and a transmembrane domain. This gene has been implicated in both Ellis-van Creveld syndrome (EvC) and Weyers acrodental dysostosis. [provided by RefSeq, Jul 2008]

EVC Gene-Disease associations (from GenCC):

acrofacial dysostosis, Weyers type
Inheritance: AD, Unknown, AR Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
Ellis-van Creveld syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health

EVC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04316947).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153717.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EVC	NM_153717.3	MANE Select	c.14G>A	p.Gly5Glu	missense	Exon 1 of 21	NP_714928.1	P57679
EVC	NM_001306090.2		c.14G>A	p.Gly5Glu	missense	Exon 1 of 21	NP_001293019.1
EVC	NM_001306092.2		c.14G>A	p.Gly5Glu	missense	Exon 1 of 12	NP_001293021.1	E9PCN4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EVC	ENST00000264956.11	TSL:1 MANE Select	c.14G>A	p.Gly5Glu	missense	Exon 1 of 21	ENSP00000264956.6	P57679
EVC	ENST00000509451.1	TSL:1	c.14G>A	p.Gly5Glu	missense	Exon 1 of 12	ENSP00000426774.1	E9PCN4
EVC	ENST00000861182.1		c.14G>A	p.Gly5Glu	missense	Exon 1 of 21	ENSP00000531241.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

865956

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

404410

African (AFR)

AF:

0.00

AC:

AN:

16394

American (AMR)

AF:

0.00

AC:

AN:

1998

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5860

East Asian (EAS)

AF:

0.00

AC:

AN:

5044

South Asian (SAS)

AF:

0.00

AC:

AN:

17556

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3238

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1772

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

785010

Other (OTH)

AF:

0.00

AC:

AN:

29084

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.0

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.061

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.42

M_CAP

Benign

0.0056

MetaRNN

Benign

0.043

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

PhyloP100

-3.5

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.97

REVEL

Benign

0.017

Sift

Benign

0.51

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.065

MutPred

0.18

Loss of MoRF binding (P = 0.0079)

MVP

0.20

ClinPred

0.099

GERP RS

-4.2

PromoterAI

-0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.039

gMVP

0.12

Mutation Taster

=99/1

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over