4-5729431-C-T

Variant names:

• chr4-5729431-C-T
• rs113870218
• NM_153717.3:c.384+41C>T

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: -1.70
• Publications: 3 publications found

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: Labcorp Genetics (formerly Invitae), Orphanet, Myriad Women’s Health

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
EVC	NM_153717.3	c.384+41C>T		intron_variant	Intron 3 of 20	ENST00000264956.11	NP_714928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVC	ENST00000264956.11	c.384+41C>T		intron_variant	Intron 3 of 20	1	NM_153717.3	ENSP00000264956.6
EVC	ENST00000509451.1	c.384+41C>T		intron_variant	Intron 3 of 11	1		ENSP00000426774.1

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

GnomAD2 exomes AF: 0.0908 AC: 22800 AN: 251230 AF XY: 0.0945

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 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

African (AFR) AF: 0.0458 AC: 1481 AN: 32358

American (AMR) AF: 0.0516 AC: 2304 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 4665 AN: 25842

East Asian (EAS) AF: 0.000304 AC: 12 AN: 39498

South Asian (SAS) AF: 0.0961 AC: 8195 AN: 85262

European-Finnish (FIN) AF: 0.103 AC: 5522 AN: 53376

Middle Eastern (MID) AF: 0.140 AC: 793 AN: 5676

European-Non Finnish (NFE) AF: 0.109 AC: 116607 AN: 1068900

Other (OTH) AF: 0.100 AC: 5888 AN: 58894

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

African (AFR) AF: 0.0478 AC: 1983 AN: 41498

American (AMR) AF: 0.0655 AC: 999 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 585 AN: 3470

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5160

South Asian (SAS) AF: 0.0893 AC: 430 AN: 4814

European-Finnish (FIN) AF: 0.106 AC: 1112 AN: 10536

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7420 AN: 67992

Other (OTH) AF: 0.0940 AC: 198 AN: 2106

Alfa AF: 0.104 Hom.: 279

Bravo AF: 0.0812

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 07, 2018

GeneDx

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

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

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	-0.86
CADD	Benign	0.22
DANN	Benign	0.53
PhyloP100		-1.7
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: rs113870218; hg19: chr4-5731158; COSMIC: COSV53839828;