rs2279250

Variant names:

• chr4-5810468-A-G
• rs2279250
• NM_153717.3:c.2894+18A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-5810468-A-G
• chr4-5810468-A-T
• chr4-5810468-A-C

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.2894+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 1,588,286 control chromosomes in the GnomAD database, including 422,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (39504 hom., cov: 33)
  • Exomes 𝑓: 0.73 (382621 hom.)
• Consequence: EVC NM_153717.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.0510
• Publications: 13 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 4-5810468-A-G is Benign according to our data. Variant chr4-5810468-A-G is described in ClinVar as Benign. ClinVar VariationId is 262778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.809 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.2894+18A>G		intron	N/A	NP_714928.1	P57679
	EVC	NM_001306090.2		c.2894+18A>G		intron	N/A	NP_001293019.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVC	ENST00000264956.11	TSL:1 MANE Select	c.2894+18A>G		intron	N/A	ENSP00000264956.6	P57679
	EVC	ENST00000861182.1		c.2894+18A>G		intron	N/A	ENSP00000531241.1
	EVC	ENST00000960562.1		c.2756+18A>G		intron	N/A	ENSP00000630621.1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109313 AN: 151960 Hom.: 39471 Cov.: 33

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.698

GnomAD2 exomes AF: 0.720 AC: 156622 AN: 217576 AF XY: 0.729

Gnomad AFR exome AF: 0.720

Gnomad AMR exome AF: 0.639

Gnomad ASJ exome AF: 0.686

Gnomad EAS exome AF: 0.560

Gnomad FIN exome AF: 0.770

Gnomad NFE exome AF: 0.732

Gnomad OTH exome AF: 0.714

GnomAD4 exome AF: 0.729 AC: 1046455 AN: 1436208 Hom.: 382621 Cov.: 29 AF XY: 0.732 AC XY: 521588 AN XY: 712766

African (AFR) AF: 0.718 AC: 23802 AN: 33150

American (AMR) AF: 0.644 AC: 26488 AN: 41128

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 17575 AN: 25596

East Asian (EAS) AF: 0.548 AC: 21449 AN: 39122

South Asian (SAS) AF: 0.835 AC: 69118 AN: 82764

European-Finnish (FIN) AF: 0.766 AC: 39984 AN: 52200

Middle Eastern (MID) AF: 0.689 AC: 3892 AN: 5648

European-Non Finnish (NFE) AF: 0.731 AC: 801753 AN: 1097142

Other (OTH) AF: 0.713 AC: 42394 AN: 59458

GnomAD4 genome AF: 0.719 AC: 109400 AN: 152078 Hom.: 39504 Cov.: 33 AF XY: 0.722 AC XY: 53680 AN XY: 74332

African (AFR) AF: 0.709 AC: 29434 AN: 41490

American (AMR) AF: 0.680 AC: 10386 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2373 AN: 3468

East Asian (EAS) AF: 0.562 AC: 2891 AN: 5142

South Asian (SAS) AF: 0.831 AC: 4000 AN: 4814

European-Finnish (FIN) AF: 0.777 AC: 8224 AN: 10582

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.731 AC: 49670 AN: 67992

Other (OTH) AF: 0.694 AC: 1462 AN: 2108

Alfa AF: 0.712 Hom.: 51336

Bravo AF: 0.705

Asia WGS AF: 0.708 AC: 2466 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	1	Curry-Hall syndrome (1)
-	-	1	Ellis-van Creveld 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	-0.94
CADD	Benign	3.8
DANN	Benign	0.42
PhyloP100		-0.051
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: rs2279250; hg19: chr4-5812195; COSMIC: COSV53833309;