rs73795089

Variant names:

• chr4-5802018-G-A
• rs73795089
• NM_153717.3:c.2373G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-5802018-G-A
• chr4-5802018-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_153717.3(EVC):​c.2373G>A​(p.Gln791Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,614,216 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (31 hom., cov: 34)
  • Exomes 𝑓: 0.0011 (20 hom.)
• Consequence: EVC NM_153717.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.350
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 4-5802018-G-A is Benign according to our data. Variant chr4-5802018-G-A is described in ClinVar as Benign. ClinVar VariationId is 349201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.35 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0108 (1650/152348) while in subpopulation AFR AF = 0.0375 (1559/41584). AF 95% confidence interval is 0.0359. There are 31 homozygotes in GnomAd4. There are 770 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 31 AD,Unknown,AR gene

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.2373G>A	p.Gln791Gln	synonymous	Exon 16 of 21	NP_714928.1
	EVC	NM_001306090.2		c.2373G>A	p.Gln791Gln	synonymous	Exon 16 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.2373G>A	p.Gln791Gln	synonymous	Exon 16 of 21	ENSP00000264956.6
	EVC	ENST00000861182.1		c.2373G>A	p.Gln791Gln	synonymous	Exon 16 of 21	ENSP00000531241.1
	EVC	ENST00000960562.1		c.2235G>A	p.Gln745Gln	synonymous	Exon 15 of 20	ENSP00000630621.1

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1642 AN: 152230 Hom.: 31 Cov.: 34

Gnomad AFR AF: 0.0374

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00353

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00275 AC: 692 AN: 251360 AF XY: 0.00220

Gnomad AFR exome AF: 0.0375

Gnomad AMR exome AF: 0.00159

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00114 AC: 1665 AN: 1461868 Hom.: 20 Cov.: 50 AF XY: 0.00103 AC XY: 746 AN XY: 727238

African (AFR) AF: 0.0392 AC: 1314 AN: 33480

American (AMR) AF: 0.00197 AC: 88 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00382 AC: 22 AN: 5754

European-Non Finnish (NFE) AF: 0.0000638 AC: 71 AN: 1112006

Other (OTH) AF: 0.00273 AC: 165 AN: 60392

GnomAD4 genome AF: 0.0108 AC: 1650 AN: 152348 Hom.: 31 Cov.: 34 AF XY: 0.0103 AC XY: 770 AN XY: 74484

African (AFR) AF: 0.0375 AC: 1559 AN: 41584

American (AMR) AF: 0.00353 AC: 54 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68038

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.00549 Hom.: 8

Bravo AF: 0.0119

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000296

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.81
DANN	Benign	0.79
PhyloP100		-0.35
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: rs73795089; hg19: chr4-5803745;