dbSNP rs4642178: EVC:c.1465-47A>C (chr4-5756217-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153717.3(EVC):c.1465-47A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,469,970 control chromosomes in the GnomAD database, including 33,393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3182 hom., cov: 31)

Exomes 𝑓: 0.21 ( 30211 hom. )

Consequence

EVC
NM_153717.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.637

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 4-5756217-A-C is Benign according to our data. Variant chr4-5756217-A-C is described in ClinVar as Benign. ClinVar VariationId is 262767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.243 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EVC	NM_153717.3	MANE Select	c.1465-47A>C	intron	N/A	NP_714928.1	P57679
EVC	NM_001306090.2		c.1465-47A>C	intron	N/A	NP_001293019.1
EVC	NM_001306092.2		c.1465-47A>C	intron	N/A	NP_001293021.1	E9PCN4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EVC	ENST00000264956.11	TSL:1 MANE Select	c.1465-47A>C	intron	N/A	ENSP00000264956.6	P57679
EVC	ENST00000509451.1	TSL:1	c.1465-47A>C	intron	N/A	ENSP00000426774.1	E9PCN4
EVC	ENST00000861182.1		c.1465-47A>C	intron	N/A	ENSP00000531241.1

Frequencies

GnomAD3 genomes

AF:

0.202

AC:

30622

AN:

151516

Hom.:

3178

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.208

GnomAD2 exomes

AF:

0.223

AC:

38362

AN:

172142

AF XY:

0.222

show subpopulations

Gnomad AFR exome

AF:

0.161

Gnomad AMR exome

AF:

0.295

Gnomad ASJ exome

AF:

0.173

Gnomad EAS exome

AF:

0.191

Gnomad FIN exome

AF:

0.236

Gnomad NFE exome

AF:

0.215

Gnomad OTH exome

AF:

0.228

GnomAD4 exome

AF:

0.209

AC:

275309

AN:

1318336

Hom.:

30211

Cov.:

AF XY:

0.210

AC XY:

137555

AN XY:

656224

show subpopulations

African (AFR)

AF:

0.162

AC:

4957

AN:

30620

American (AMR)

AF:

0.291

AC:

10690

AN:

36688

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

4163

AN:

24656

East Asian (EAS)

AF:

0.187

AC:

7048

AN:

37660

South Asian (SAS)

AF:

0.222

AC:

17027

AN:

76540

European-Finnish (FIN)

AF:

0.242

AC:

11975

AN:

49518

Middle Eastern (MID)

AF:

0.249

AC:

1372

AN:

5520

European-Non Finnish (NFE)

AF:

0.206

AC:

206846

AN:

1001752

Other (OTH)

AF:

0.203

AC:

11231

AN:

55382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

11123

22245

33368

44490

55613

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6910

13820

20730

27640

34550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.202

AC:

30652

AN:

151634

Hom.:

3182

Cov.:

AF XY:

0.205

AC XY:

15172

AN XY:

74074

show subpopulations

African (AFR)

AF:

0.160

AC:

6605

AN:

41364

American (AMR)

AF:

0.250

AC:

3808

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

581

AN:

3466

East Asian (EAS)

AF:

0.181

AC:

933

AN:

5150

South Asian (SAS)

AF:

0.223

AC:

1074

AN:

4806

European-Finnish (FIN)

AF:

0.224

AC:

2338

AN:

10420

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.215

AC:

14618

AN:

67870

Other (OTH)

AF:

0.205

AC:

433

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

1271

2542

3813

5084

6355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

342

684

1026

1368

1710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.199

Hom.:

557

Bravo

AF:

0.202

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Ellis-van Creveld syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.28

(source)

DANN

Benign

0.66

PhyloP100

-0.64

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over