dbSNP rs546318095: EVC:c.-35C>A (chr4-5711346-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_153717.3(EVC):c.-35C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00594 in 1,006,604 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0065 ( 20 hom. )

Consequence

EVC
NM_153717.3 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0920

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BS2

High Homozygotes in GnomAdExome4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC	NM_153717.3 link	c.-35C>A		5_prime_UTR_variant	Exon 1 of 21	ENST00000264956.11	NP_714928.1	P57679

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVC	ENST00000264956 link	c.-35C>A		5_prime_UTR_variant	Exon 1 of 21	1	NM_153717.3	ENSP00000264956.6		P57679
EVC	ENST00000509451 link	c.-35C>A		5_prime_UTR_variant	Exon 1 of 12	1		ENSP00000426774.1		E9PCN4

Frequencies

GnomAD3 genomes

AF:

0.00275

AC:

414

AN:

150808

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000872

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000925

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000200

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00520

Gnomad OTH

AF:

0.00193

GnomAD3 exomes

AF:

0.00730

AC:

AN:

274

Hom.:

AF XY:

0.0130

AC XY:

AN XY:

154

show subpopulations

Gnomad NFE exome

AF:

0.00746

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00650

AC:

5564

AN:

855688

Hom.:

Cov.:

AF XY:

0.00653

AC XY:

2597

AN XY:

397772

show subpopulations

Gnomad4 AFR exome

AF:

0.000738

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.00105

Gnomad4 EAS exome

AF:

0.000209

Gnomad4 SAS exome

AF:

0.0000582

Gnomad4 FIN exome

AF:

0.00115

Gnomad4 NFE exome

AF:

0.00691

Gnomad4 OTH exome

AF:

0.00580

GnomAD4 genome

AF:

0.00274

AC:

414

AN:

150916

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

184

AN XY:

73774

show subpopulations

Gnomad4 AFR

AF:

0.000870

Gnomad4 AMR

AF:

0.000924

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000200

Gnomad4 NFE

AF:

0.00521

Gnomad4 OTH

AF:

0.00191

Alfa

AF:

0.000374

Hom.:

Bravo

AF:

0.00300

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Ellis-van Creveld syndrome

Uncertain:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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

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