NM_153717.3:c.2298C>T

Variant names:

• chr4-5798786-C-T
• rs140546984
• NM_153717.3:c.2298C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_153717.3(EVC):​c.2298C>T​(p.Asp766Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,610,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: EVC NM_153717.3 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: 0.454
• 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]

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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 4-5798786-C-T is Benign according to our data. Variant chr4-5798786-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 262772.
• BP7: Synonymous conserved (PhyloP=0.454 with no splicing effect.

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.2298C>T	p.Asp766Asp	synonymous	Exon 15 of 21	NP_714928.1	P57679
	EVC	NM_001306090.2		c.2298C>T	p.Asp766Asp	synonymous	Exon 15 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.2298C>T	p.Asp766Asp	synonymous	Exon 15 of 21	ENSP00000264956.6	P57679
	EVC	ENST00000861182.1		c.2298C>T	p.Asp766Asp	synonymous	Exon 15 of 21	ENSP00000531241.1
	EVC	ENST00000960562.1		c.2160C>T	p.Asp720Asp	synonymous	Exon 14 of 20	ENSP00000630621.1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152206 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000210 AC: 51 AN: 242958 AF XY: 0.000256

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000874

Gnomad ASJ exome AF: 0.00262

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000148

Gnomad OTH exome AF: 0.000497

GnomAD4 exome AF: 0.000106 AC: 155 AN: 1458440 Hom.: 0 Cov.: 32 AF XY: 0.000109 AC XY: 79 AN XY: 725462

African (AFR) AF: 0.0000599 AC: 2 AN: 33410

American (AMR) AF: 0.0000895 AC: 4 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00237 AC: 62 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000349 AC: 3 AN: 85958

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52388

Middle Eastern (MID) AF: 0.00192 AC: 8 AN: 4176

European-Non Finnish (NFE) AF: 0.0000504 AC: 56 AN: 1111828

Other (OTH) AF: 0.000332 AC: 20 AN: 60196

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152324 Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13 AN XY: 74486

African (AFR) AF: 0.00 AC: 0 AN: 41586

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68018

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000280 Hom.: 0

Bravo AF: 0.0000869

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000238

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.6
DANN	Benign	0.67
PhyloP100		0.45
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: rs140546984; hg19: chr4-5800513;