rs2291151

Variant names:

• chr4-5811051-G-A
• rs2291151
• NM_153717.3:c.*14G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-5811051-G-A
• chr4-5811051-G-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.*14G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,600,302 control chromosomes in the GnomAD database, including 294,057 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (27977 hom., cov: 33)
  • Exomes 𝑓: 0.60 (266080 hom.)
• Consequence: EVC NM_153717.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.778
• Publications: 15 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 4-5811051-G-A is Benign according to our data. Variant chr4-5811051-G-A is described in ClinVar as Benign. ClinVar VariationId is 262759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 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.*14G>A		3_prime_UTR	Exon 21 of 21	NP_714928.1	P57679
	EVC	NM_001306090.2		c.*14G>A		3_prime_UTR	Exon 21 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.*14G>A		3_prime_UTR	Exon 21 of 21	ENSP00000264956.6	P57679
	EVC	ENST00000861182.1		c.*14G>A		3_prime_UTR	Exon 21 of 21	ENSP00000531241.1
	EVC	ENST00000960562.1		c.*14G>A		3_prime_UTR	Exon 20 of 20	ENSP00000630621.1

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91736 AN: 151946 Hom.: 27948 Cov.: 33

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.589

GnomAD2 exomes AF: 0.579 AC: 136742 AN: 236022 AF XY: 0.587

Gnomad AFR exome AF: 0.629

Gnomad AMR exome AF: 0.446

Gnomad ASJ exome AF: 0.600

Gnomad EAS exome AF: 0.339

Gnomad FIN exome AF: 0.693

Gnomad NFE exome AF: 0.615

Gnomad OTH exome AF: 0.589

GnomAD4 exome AF: 0.603 AC: 872793 AN: 1448238 Hom.: 266080 Cov.: 30 AF XY: 0.604 AC XY: 434708 AN XY: 719906

African (AFR) AF: 0.628 AC: 20739 AN: 32998

American (AMR) AF: 0.454 AC: 19892 AN: 43810

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 15693 AN: 26024

East Asian (EAS) AF: 0.318 AC: 12356 AN: 38902

South Asian (SAS) AF: 0.629 AC: 52967 AN: 84240

European-Finnish (FIN) AF: 0.682 AC: 36128 AN: 52936

Middle Eastern (MID) AF: 0.617 AC: 3538 AN: 5738

European-Non Finnish (NFE) AF: 0.612 AC: 675824 AN: 1103722

Other (OTH) AF: 0.596 AC: 35656 AN: 59868

GnomAD4 genome AF: 0.604 AC: 91810 AN: 152064 Hom.: 27977 Cov.: 33 AF XY: 0.604 AC XY: 44904 AN XY: 74296

African (AFR) AF: 0.627 AC: 26023 AN: 41494

American (AMR) AF: 0.531 AC: 8115 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2085 AN: 3472

East Asian (EAS) AF: 0.331 AC: 1703 AN: 5148

South Asian (SAS) AF: 0.604 AC: 2903 AN: 4808

European-Finnish (FIN) AF: 0.701 AC: 7410 AN: 10572

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.613 AC: 41665 AN: 67978

Other (OTH) AF: 0.585 AC: 1235 AN: 2110

Alfa AF: 0.582 Hom.: 14367

Bravo AF: 0.586

Asia WGS AF: 0.484 AC: 1688 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Ellis-van Creveld syndrome (2)
-	-	1	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	0.26
DANN	Benign	0.54
PhyloP100		-0.78
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: rs2291151; hg19: chr4-5812778; COSMIC: COSV53830500;