4-5745189-C-T

Variant names:

• chr4-5745189-C-T
• rs4689313
• NM_153717.3:c.802-15C>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.802-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 1,518,254 control chromosomes in the GnomAD database, including 280,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (23607 hom., cov: 30)
  • Exomes 𝑓: 0.62 (257232 hom.)
• Consequence: EVC NM_153717.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.653
• Publications: 5 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: AR, Unknown, AD Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• Ellis-van Creveld syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-5745189-C-T is Benign according to our data. Variant chr4-5745189-C-T is described in ClinVar as Benign. ClinVar VariationId is 262782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVC	NM_153717.3	MANE Select	c.802-15C>T		intron	N/A	NP_714928.1	P57679
	EVC	NM_001306090.2		c.802-15C>T		intron	N/A	NP_001293019.1
	EVC	NM_001306092.2		c.802-15C>T		intron	N/A	NP_001293021.1	E9PCN4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVC	ENST00000264956.11	TSL:1 MANE Select	c.802-15C>T		intron	N/A	ENSP00000264956.6	P57679
	EVC	ENST00000509451.1	TSL:1	c.802-15C>T		intron	N/A	ENSP00000426774.1	E9PCN4
	EVC	ENST00000861182.1		c.802-15C>T		intron	N/A	ENSP00000531241.1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 83911 AN: 139246 Hom.: 23594 Cov.: 30

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.597

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.591

GnomAD2 exomes AF: 0.597 AC: 141222 AN: 236632 AF XY: 0.600

Gnomad AFR exome AF: 0.643

Gnomad AMR exome AF: 0.459

Gnomad ASJ exome AF: 0.672

Gnomad EAS exome AF: 0.348

Gnomad FIN exome AF: 0.652

Gnomad NFE exome AF: 0.662

Gnomad OTH exome AF: 0.625

GnomAD4 exome AF: 0.623 AC: 859465 AN: 1378912 Hom.: 257232 Cov.: 34 AF XY: 0.622 AC XY: 426832 AN XY: 686316

African (AFR) AF: 0.596 AC: 16171 AN: 27150

American (AMR) AF: 0.461 AC: 19304 AN: 41882

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 16078 AN: 24626

East Asian (EAS) AF: 0.337 AC: 13351 AN: 39592

South Asian (SAS) AF: 0.567 AC: 46101 AN: 81308

European-Finnish (FIN) AF: 0.627 AC: 31735 AN: 50586

Middle Eastern (MID) AF: 0.581 AC: 3085 AN: 5312

European-Non Finnish (NFE) AF: 0.645 AC: 678689 AN: 1051860

Other (OTH) AF: 0.618 AC: 34951 AN: 56596

GnomAD4 genome AF: 0.603 AC: 83979 AN: 139342 Hom.: 23607 Cov.: 30 AF XY: 0.597 AC XY: 40714 AN XY: 68152

African (AFR) AF: 0.597 AC: 20487 AN: 34314

American (AMR) AF: 0.529 AC: 7561 AN: 14300

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2129 AN: 3302

East Asian (EAS) AF: 0.350 AC: 1800 AN: 5148

South Asian (SAS) AF: 0.569 AC: 2627 AN: 4616

European-Finnish (FIN) AF: 0.633 AC: 6276 AN: 9910

Middle Eastern (MID) AF: 0.607 AC: 165 AN: 272

European-Non Finnish (NFE) AF: 0.638 AC: 41315 AN: 64708

Other (OTH) AF: 0.592 AC: 1142 AN: 1930

Alfa AF: 0.00181 Hom.: 6

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Ellis-van Creveld syndrome (3)
-	-	2	not specified (2)
-	-	1	Curry-Hall syndrome (1)
-	-	1	Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.16
DANN	Benign	0.37
PhyloP100		-0.65
Mutation Taster		=16/84	disease causing

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: rs4689313; hg19: chr4-5746916; COSMIC: COSV53830453; COSMIC: COSV53830453;