rs4688963

Variant names:

• chr4-5748177-T-C
• rs4688963
• NM_153717.3:c.969T>C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_153717.3(EVC):​c.969T>C​(p.Asn323Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,613,814 control chromosomes in the GnomAD database, including 132,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13248 hom., cov: 33)
  • Exomes 𝑓: 0.40 (119027 hom.)
• Consequence: EVC NM_153717.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.892
• Publications: 25 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 4-5748177-T-C is Benign according to our data. Variant chr4-5748177-T-C is described in ClinVar as Benign. ClinVar VariationId is 262786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.892 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 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.969T>C	p.Asn323Asn	synonymous	Exon 8 of 21	NP_714928.1	P57679
	EVC	NM_001306090.2		c.969T>C	p.Asn323Asn	synonymous	Exon 8 of 21	NP_001293019.1
	EVC	NM_001306092.2		c.969T>C	p.Asn323Asn	synonymous	Exon 8 of 12	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.969T>C	p.Asn323Asn	synonymous	Exon 8 of 21	ENSP00000264956.6	P57679
	EVC	ENST00000509451.1	TSL:1	c.969T>C	p.Asn323Asn	synonymous	Exon 8 of 12	ENSP00000426774.1	E9PCN4
	EVC	ENST00000861182.1		c.969T>C	p.Asn323Asn	synonymous	Exon 8 of 21	ENSP00000531241.1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62557 AN: 151918 Hom.: 13226 Cov.: 33

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.391

GnomAD2 exomes AF: 0.413 AC: 103901 AN: 251444 AF XY: 0.419

Gnomad AFR exome AF: 0.472

Gnomad AMR exome AF: 0.340

Gnomad ASJ exome AF: 0.358

Gnomad EAS exome AF: 0.624

Gnomad FIN exome AF: 0.394

Gnomad NFE exome AF: 0.370

Gnomad OTH exome AF: 0.377

GnomAD4 exome AF: 0.399 AC: 582821 AN: 1461778 Hom.: 119027 Cov.: 50 AF XY: 0.403 AC XY: 292996 AN XY: 727196

African (AFR) AF: 0.475 AC: 15917 AN: 33476

American (AMR) AF: 0.338 AC: 15136 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 9284 AN: 26134

East Asian (EAS) AF: 0.642 AC: 25476 AN: 39700

South Asian (SAS) AF: 0.538 AC: 46407 AN: 86254

European-Finnish (FIN) AF: 0.391 AC: 20877 AN: 53392

Middle Eastern (MID) AF: 0.392 AC: 2259 AN: 5768

European-Non Finnish (NFE) AF: 0.380 AC: 422955 AN: 1111934

Other (OTH) AF: 0.406 AC: 24510 AN: 60396

GnomAD4 genome AF: 0.412 AC: 62625 AN: 152036 Hom.: 13248 Cov.: 33 AF XY: 0.417 AC XY: 30966 AN XY: 74304

African (AFR) AF: 0.472 AC: 19586 AN: 41458

American (AMR) AF: 0.345 AC: 5276 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1228 AN: 3470

East Asian (EAS) AF: 0.626 AC: 3230 AN: 5158

South Asian (SAS) AF: 0.532 AC: 2559 AN: 4810

European-Finnish (FIN) AF: 0.408 AC: 4303 AN: 10546

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25121 AN: 67992

Other (OTH) AF: 0.397 AC: 836 AN: 2108

Alfa AF: 0.378 Hom.: 17509

Bravo AF: 0.410

Asia WGS AF: 0.549 AC: 1909 AN: 3478

EpiCase AF: 0.369

EpiControl AF: 0.380

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)
-	-	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	-0.43
CADD	Benign	16
DANN	Benign	0.76
PhyloP100		0.89
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: rs4688963; hg19: chr4-5749904; COSMIC: COSV53833510; COSMIC: COSV53833510;