NM_153717.3:c.1854C>T

Variant names:

• chr4-5793685-C-T
• rs11737221
• NM_153717.3:c.1854C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_153717.3(EVC):​c.1854C>T​(p.Gly618Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,550,636 control chromosomes in the GnomAD database, including 87,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G618G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.27 (6782 hom., cov: 32)
  • Exomes 𝑓: 0.33 (80949 hom.)
• Consequence: EVC NM_153717.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -1.80
• Publications: 21 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]

CRMP1 (HGNC:2365): (collapsin response mediator protein 1) This gene encodes a member of a family of cytosolic phosphoproteins expressed exclusively in the nervous system. The encoded protein is thought to be a part of the semaphorin signal transduction pathway implicated in semaphorin-induced growth cone collapse during neural development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 4-5793685-C-T is Benign according to our data. Variant chr4-5793685-C-T is described in ClinVar as Benign. ClinVar VariationId is 262769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.8 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.517 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.1854C>T	p.Gly618Gly	synonymous	Exon 13 of 21	NP_714928.1	P57679
	EVC	NM_001306090.2		c.1854C>T	p.Gly618Gly	synonymous	Exon 13 of 21	NP_001293019.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVC	ENST00000264956.11	TSL:1 MANE Select	c.1854C>T	p.Gly618Gly	synonymous	Exon 13 of 21	ENSP00000264956.6	P57679
	EVC	ENST00000861182.1		c.1854C>T	p.Gly618Gly	synonymous	Exon 13 of 21	ENSP00000531241.1
	EVC	ENST00000960562.1		c.1716C>T	p.Gly572Gly	synonymous	Exon 12 of 20	ENSP00000630621.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41578 AN: 151892 Hom.: 6776 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.284

GnomAD2 exomes AF: 0.355 AC: 55868 AN: 157544 AF XY: 0.369

Gnomad AFR exome AF: 0.0953

Gnomad AMR exome AF: 0.345

Gnomad ASJ exome AF: 0.314

Gnomad EAS exome AF: 0.514

Gnomad FIN exome AF: 0.319

Gnomad NFE exome AF: 0.319

Gnomad OTH exome AF: 0.337

GnomAD4 exome AF: 0.333 AC: 465360 AN: 1398626 Hom.: 80949 Cov.: 37 AF XY: 0.339 AC XY: 233910 AN XY: 689968

African (AFR) AF: 0.0979 AC: 3108 AN: 31738

American (AMR) AF: 0.341 AC: 12223 AN: 35866

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 7660 AN: 25184

East Asian (EAS) AF: 0.504 AC: 18100 AN: 35884

South Asian (SAS) AF: 0.520 AC: 41229 AN: 79214

European-Finnish (FIN) AF: 0.319 AC: 15743 AN: 49354

Middle Eastern (MID) AF: 0.333 AC: 1448 AN: 4354

European-Non Finnish (NFE) AF: 0.321 AC: 346699 AN: 1079140

Other (OTH) AF: 0.331 AC: 19150 AN: 57892

GnomAD4 genome AF: 0.274 AC: 41603 AN: 152010 Hom.: 6782 Cov.: 32 AF XY: 0.283 AC XY: 21037 AN XY: 74272

African (AFR) AF: 0.103 AC: 4265 AN: 41508

American (AMR) AF: 0.318 AC: 4863 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1075 AN: 3472

East Asian (EAS) AF: 0.518 AC: 2657 AN: 5134

South Asian (SAS) AF: 0.534 AC: 2565 AN: 4804

European-Finnish (FIN) AF: 0.319 AC: 3366 AN: 10546

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21812 AN: 67958

Other (OTH) AF: 0.282 AC: 596 AN: 2116

Alfa AF: 0.224 Hom.: 1410

Bravo AF: 0.265

Asia WGS AF: 0.481 AC: 1671 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Ellis-van Creveld syndrome (3)
-	-	2	not provided (2)
-	-	1	Curry-Hall syndrome (1)
-	-	1	Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.7
DANN	Benign	0.80
PhyloP100		-1.8
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: rs11737221; hg19: chr4-5795412; COSMIC: COSV53832761;