rs1031919

Variant names:

• chr4-5801942-T-C
• rs1031919
• NM_153717.3:c.2305-8T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-5801942-T-C
• chr4-5801942-T-G

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.2305-8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,612,074 control chromosomes in the GnomAD database, including 432,017 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (39628 hom., cov: 33)
  • Exomes 𝑓: 0.73 (392389 hom.)
• Consequence: EVC NM_153717.3 splice_region, intron
• Scores: Splicing: ADA: 0.00005523
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -1.05
• 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=-0.9).
• BP6: Variant 4-5801942-T-C is Benign according to our data. Variant chr4-5801942-T-C is described in ClinVar as Benign. ClinVar VariationId is 262774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC	NM_153717.3	c.2305-8T>C		splice_region_variant, intron_variant	Intron 15 of 20	ENST00000264956.11	NP_714928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVC	ENST00000264956.11	c.2305-8T>C		splice_region_variant, intron_variant	Intron 15 of 20	1	NM_153717.3	ENSP00000264956.6
CRMP1	ENST00000506216.5	n.1647+23552A>G		intron_variant	Intron 12 of 12	5
EVC	ENST00000515113.1	n.*135T>C		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109631 AN: 152034 Hom.: 39592 Cov.: 33

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.704

GnomAD2 exomes AF: 0.719 AC: 179567 AN: 249798 AF XY: 0.727

Gnomad AFR exome AF: 0.716

Gnomad AMR exome AF: 0.644

Gnomad ASJ exome AF: 0.685

Gnomad EAS exome AF: 0.549

Gnomad FIN exome AF: 0.783

Gnomad NFE exome AF: 0.733

Gnomad OTH exome AF: 0.715

GnomAD4 exome AF: 0.732 AC: 1068320 AN: 1459922 Hom.: 392389 Cov.: 53 AF XY: 0.734 AC XY: 533351 AN XY: 726242

African (AFR) AF: 0.708 AC: 23682 AN: 33438

American (AMR) AF: 0.650 AC: 28970 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 17807 AN: 26114

East Asian (EAS) AF: 0.537 AC: 21306 AN: 39682

South Asian (SAS) AF: 0.819 AC: 70540 AN: 86132

European-Finnish (FIN) AF: 0.776 AC: 41395 AN: 53368

Middle Eastern (MID) AF: 0.699 AC: 3418 AN: 4890

European-Non Finnish (NFE) AF: 0.736 AC: 818123 AN: 1111474

Other (OTH) AF: 0.715 AC: 43079 AN: 60254

GnomAD4 genome AF: 0.721 AC: 109717 AN: 152152 Hom.: 39628 Cov.: 33 AF XY: 0.724 AC XY: 53850 AN XY: 74406

African (AFR) AF: 0.709 AC: 29404 AN: 41486

American (AMR) AF: 0.685 AC: 10481 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2333 AN: 3472

East Asian (EAS) AF: 0.552 AC: 2844 AN: 5152

South Asian (SAS) AF: 0.811 AC: 3912 AN: 4824

European-Finnish (FIN) AF: 0.788 AC: 8358 AN: 10606

Middle Eastern (MID) AF: 0.668 AC: 195 AN: 292

European-Non Finnish (NFE) AF: 0.734 AC: 49944 AN: 68000

Other (OTH) AF: 0.698 AC: 1476 AN: 2114

Alfa AF: 0.728 Hom.: 17451

Bravo AF: 0.708

Asia WGS AF: 0.678 AC: 2358 AN: 3478

EpiCase AF: 0.718

EpiControl AF: 0.722

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Mar 03, 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. -

-

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

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:3

Jan 12, 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. -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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	-0.90
CADD	Benign	0.93
DANN	Benign	0.61
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000055
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.010		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: rs1031919; hg19: chr4-5803669; COSMIC: COSV53830478; COSMIC: COSV53830478;