NM_153717.3:c.802-5_802-3delTTC

Variant names:

• chr4-5745186-TTTC-T
• rs370315662
• NM_153717.3:c.802-5_802-3delTTC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_153717.3(EVC):​c.802-5_802-3delTTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,570,128 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00057 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000088 (0 hom.)
• Consequence: EVC NM_153717.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.526
• Publications: 0 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 -8 ACMG points.

• BP6: Variant 4-5745186-TTTC-T is Benign according to our data. Variant chr4-5745186-TTTC-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVC	NM_153717.3	MANE Select	c.802-5_802-3delTTC		splice_region intron	N/A	NP_714928.1
	EVC	NM_001306090.2		c.802-5_802-3delTTC		splice_region intron	N/A	NP_001293019.1
	EVC	NM_001306092.2		c.802-5_802-3delTTC		splice_region intron	N/A	NP_001293021.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVC	ENST00000264956.11	TSL:1 MANE Select	c.802-5_802-3delTTC		splice_region intron	N/A	ENSP00000264956.6
	EVC	ENST00000509451.1	TSL:1	c.802-5_802-3delTTC		splice_region intron	N/A	ENSP00000426774.1

Frequencies

GnomAD3 genomes AF: 0.000571 AC: 70 AN: 122686 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000225

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000338

Gnomad OTH AF: 0.00120

GnomAD2 exomes AF: 0.000160 AC: 39 AN: 243116 AF XY: 0.000114

Gnomad AFR exome AF: 0.00188

Gnomad AMR exome AF: 0.000118

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000110

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000543

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000877 AC: 127 AN: 1447442 Hom.: 0 AF XY: 0.0000861 AC XY: 62 AN XY: 720100

African (AFR) AF: 0.00152 AC: 48 AN: 31658

American (AMR) AF: 0.000293 AC: 13 AN: 44314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25880

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39662

South Asian (SAS) AF: 0.000106 AC: 9 AN: 84942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53090

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5666

European-Non Finnish (NFE) AF: 0.0000345 AC: 38 AN: 1102484

Other (OTH) AF: 0.000218 AC: 13 AN: 59746

GnomAD4 genome AF: 0.000571 AC: 70 AN: 122686 Hom.: 0 Cov.: 29 AF XY: 0.000598 AC XY: 36 AN XY: 60154

African (AFR) AF: 0.00241 AC: 62 AN: 25726

American (AMR) AF: 0.000225 AC: 3 AN: 13342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2956

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.0000338 AC: 2 AN: 59212

Other (OTH) AF: 0.00120 AC: 2 AN: 1662

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Oct 08, 2021

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jun 24, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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;C0457013:Curry-Hall syndrome Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism

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: rs370315662; hg19: chr4-5746913;