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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC	NM_153717.3	c.*14G>A		3_prime_UTR_variant	Exon 21 of 21	ENST00000264956.11	NP_714928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVC	ENST00000264956.11	c.*14G>A		3_prime_UTR_variant	Exon 21 of 21	1	NM_153717.3	ENSP00000264956.6
CRMP1	ENST00000506216.5	n.1647+14443C>T		intron_variant	Intron 12 of 12	5

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

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 29, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Ellis-van Creveld syndrome Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Curry-Hall syndrome Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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;