rs113870218

chr4-5729431-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153717.3(EVC):c.384+41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,566,498 control chromosomes in the GnomAD database, including 8,668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.085 (611 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8057 hom.)
• Consequence: EVC NM_153717.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.70

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 4-5729431-C-T is Benign according to our data. Variant chr4-5729431-C-T is described in ClinVar as [Benign]. Clinvar id is 262780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EVC	NM_153717.3	c.384+41C>T		intron_variant		ENST00000264956.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVC	ENST00000264956.11	c.384+41C>T		intron_variant		1	NM_153717.3	P1
EVC	ENST00000509451.1	c.384+41C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0849 AC: 12900 AN: 151912 Hom.: 610 Cov.: 32

Gnomad AFR AF: 0.0480

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.0656

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0888

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0950

GnomAD3 exomes AF: 0.0908 AC: 22800 AN: 251230 Hom.: 1222 AF XY: 0.0945 AC XY: 12833 AN XY: 135780

Gnomad AFR exome AF: 0.0490

Gnomad AMR exome AF: 0.0480

Gnomad ASJ exome AF: 0.181

Gnomad EAS exome AF: 0.000490

Gnomad SAS exome AF: 0.0953

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.0919

GnomAD4 exome AF: 0.103 AC: 145467 AN: 1414468 Hom.: 8057 Cov.: 24 AF XY: 0.104 AC XY: 73311 AN XY: 706702

Gnomad4 AFR exome AF: 0.0458

Gnomad4 AMR exome AF: 0.0516

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.000304

Gnomad4 SAS exome AF: 0.0961

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.0848 AC: 12898 AN: 152030 Hom.: 611 Cov.: 32 AF XY: 0.0826 AC XY: 6139 AN XY: 74294

Gnomad4 AFR AF: 0.0478

Gnomad4 AMR AF: 0.0655

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.0893

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.0940

Alfa AF: 0.106 Hom.: 165

Bravo AF: 0.0812

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Ellis-van Creveld syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jun 15, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.22
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: rs113870218; hg19: chr4-5731158; COSMIC: COSV53839828;