dbSNP rs113571700: EVC:c.385-16C>T (chr4-5731409-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_153717.3(EVC):c.385-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00626 in 1,599,726 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 22 hom., cov: 31)

Exomes 𝑓: 0.0058 ( 92 hom. )

Consequence

EVC
NM_153717.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0660

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 4-5731409-C-T is Benign according to our data. Variant chr4-5731409-C-T is described in ClinVar as [Benign]. Clinvar id is 262781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0104 (1582/151908) while in subpopulation SAS AF= 0.0308 (147/4772). AF 95% confidence interval is 0.0267. There are 22 homozygotes in gnomad4. There are 805 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC	NM_153717.3 link	c.385-16C>T		intron_variant	Intron 3 of 20	ENST00000264956.11	NP_714928.1	P57679

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVC	ENST00000264956.11 link	c.385-16C>T		intron_variant	Intron 3 of 20	1	NM_153717.3	ENSP00000264956.6		P57679
EVC	ENST00000509451.1 link	c.385-16C>T		intron_variant	Intron 3 of 11	1		ENSP00000426774.1		E9PCN4

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1574

AN:

151790

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00551

Gnomad ASJ

AF:

0.00894

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0308

Gnomad FIN

AF:

0.0000946

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00390

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00821

AC:

2045

AN:

249028

Hom.:

AF XY:

0.00931

AC XY:

1255

AN XY:

134826

show subpopulations

Gnomad AFR exome

AF:

0.0249

Gnomad AMR exome

AF:

0.00385

Gnomad ASJ exome

AF:

0.0127

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0271

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00450

Gnomad OTH exome

AF:

0.00655

GnomAD4 exome

AF:

0.00582

AC:

8425

AN:

1447818

Hom.:

Cov.:

AF XY:

0.00654

AC XY:

4715

AN XY:

721288

show subpopulations

Gnomad4 AFR exome

AF:

0.0287

Gnomad4 AMR exome

AF:

0.00398

Gnomad4 ASJ exome

AF:

0.0112

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0282

Gnomad4 FIN exome

AF:

0.000487

Gnomad4 NFE exome

AF:

0.00357

Gnomad4 OTH exome

AF:

0.00843

GnomAD4 genome

AF:

0.0104

AC:

1582

AN:

151908

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

805

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.0247

Gnomad4 AMR

AF:

0.00550

Gnomad4 ASJ

AF:

0.00894

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0308

Gnomad4 FIN

AF:

0.0000946

Gnomad4 NFE

AF:

0.00390

Gnomad4 OTH

AF:

0.0119

Alfa

AF:

0.00791

Hom.:

Bravo

AF:

0.0111

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Aug 01, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Oct 16, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome

Benign:1

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ellis-van Creveld syndrome

Benign:1

Jun 15, 2021

Pars Genome Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.82

DANN

Benign

0.36

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over