Genetic Variant EVC:c.2305-44C>T (chr4-5801906-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153717.3(EVC):c.2305-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,603,566 control chromosomes in the GnomAD database, including 95,310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 7063 hom., cov: 33)

Exomes 𝑓: 0.34 ( 88247 hom. )

Consequence

EVC
NM_153717.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.15

Variant links:

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]

EVC links:

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]

CRMP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 4-5801906-C-T is Benign according to our data. Variant chr4-5801906-C-T is described in ClinVar as [Benign]. Clinvar id is 262773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC	NM_153717.3 link	c.2305-44C>T		intron_variant	Intron 15 of 20	ENST00000264956.11	NP_714928.1	P57679

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EVC	ENST00000264956.11 link	c.2305-44C>T	intron_variant	Intron 15 of 20	1	NM_153717.3	ENSP00000264956.6	P57679
CRMP1	ENST00000506216.5 link	n.1647+23588G>A	intron_variant	Intron 12 of 12	5
EVC	ENST00000515113.1 link	n.*99C>T	downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42547

AN:

152064

Hom.:

7056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.439

Gnomad AMR

AF:

0.324

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.513

Gnomad SAS

AF:

0.537

Gnomad FIN

AF:

0.320

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.294

GnomAD3 exomes

AF:

0.357

AC:

85139

AN:

238712

Hom.:

16298

AF XY:

0.369

AC XY:

47544

AN XY:

128888

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.360

Gnomad ASJ exome

AF:

0.310

Gnomad EAS exome

AF:

0.515

Gnomad SAS exome

AF:

0.528

Gnomad FIN exome

AF:

0.321

Gnomad NFE exome

AF:

0.330

Gnomad OTH exome

AF:

0.343

GnomAD4 exome

AF:

0.342

AC:

495986

AN:

1451382

Hom.:

88247

Cov.:

AF XY:

0.348

AC XY:

251111

AN XY:

721344

show subpopulations

Gnomad4 AFR exome

AF:

0.100

Gnomad4 AMR exome

AF:

0.355

Gnomad4 ASJ exome

AF:

0.301

Gnomad4 EAS exome

AF:

0.504

Gnomad4 SAS exome

AF:

0.522

Gnomad4 FIN exome

AF:

0.321

Gnomad4 NFE exome

AF:

0.331

Gnomad4 OTH exome

AF:

0.338

GnomAD4 genome

AF:

0.280

AC:

42575

AN:

152184

Hom.:

7063

Cov.:

AF XY:

0.289

AC XY:

21490

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.325

Gnomad4 ASJ

AF:

0.302

Gnomad4 EAS

AF:

0.514

Gnomad4 SAS

AF:

0.537

Gnomad4 FIN

AF:

0.320

Gnomad4 NFE

AF:

0.331

Gnomad4 OTH

AF:

0.292

Alfa

AF:

0.238

Hom.:

897

Bravo

AF:

0.272

Asia WGS

AF:

0.483

AC:

1678

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.87

CADD

Benign

1.5

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over