dbSNP rs577263762: EVC:c.-36G>A (chr4-5711345-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_153717.3(EVC):c.-36G>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 0.00595 in 1,007,450 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 0.0028 ( 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: 3.00

Publications

0 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 Gene-Disease associations (from GenCC):

acrofacial dysostosis, Weyers type
Inheritance: AD, Unknown, AR Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
Ellis-van Creveld syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health

EVC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BS2

High Homozygotes in GnomAdExome4 at 20 AD,Unknown,AR gene

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.-36G>A	5_prime_UTR	Exon 1 of 21	NP_714928.1	P57679
EVC	NM_001306090.2		c.-36G>A	5_prime_UTR	Exon 1 of 21	NP_001293019.1
EVC	NM_001306092.2		c.-36G>A	5_prime_UTR	Exon 1 of 12	NP_001293021.1	E9PCN4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EVC	ENST00000264956.11	TSL:1 MANE Select	c.-36G>A	5_prime_UTR	Exon 1 of 21	ENSP00000264956.6	P57679
EVC	ENST00000509451.1	TSL:1	c.-36G>A	5_prime_UTR	Exon 1 of 12	ENSP00000426774.1	E9PCN4
EVC	ENST00000861182.1		c.-36G>A	5_prime_UTR	Exon 1 of 21	ENSP00000531241.1

Frequencies

GnomAD3 genomes

AF:

0.00276

AC:

416

AN:

150866

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:

0.000207

Gnomad FIN

AF:

0.000200

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00522

Gnomad OTH

AF:

0.00194

GnomAD2 exomes

AF:

0.00730

AC:

AN:

274

AF XY:

0.0132

show subpopulations

Gnomad NFE exome

AF:

0.00746

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00651

AC:

5574

AN:

856478

Hom.:

Cov.:

AF XY:

0.00653

AC XY:

2601

AN XY:

398168

show subpopulations

African (AFR)

AF:

0.000738

AC:

AN:

16270

American (AMR)

AF:

0.00179

AC:

AN:

1674

Ashkenazi Jewish (ASJ)

AF:

0.00105

AC:

AN:

5716

East Asian (EAS)

AF:

0.000207

AC:

AN:

4830

South Asian (SAS)

AF:

0.000349

AC:

AN:

17202

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

2660

Middle Eastern (MID)

AF:

0.000579

AC:

AN:

1726

European-Non Finnish (NFE)

AF:

0.00691

AC:

5374

AN:

777714

Other (OTH)

AF:

0.00586

AC:

168

AN:

28686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

293

586

879

1172

1465

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

276

552

828

1104

1380

<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:

0.00276

AC:

416

AN:

150972

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

185

AN XY:

73804

show subpopulations

African (AFR)

AF:

0.000869

AC:

AN:

41406

American (AMR)

AF:

0.000924

AC:

AN:

15158

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5140

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000200

AC:

AN:

10018

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00522

AC:

353

AN:

67668

Other (OTH)

AF:

0.00192

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00101

Hom.:

Bravo

AF:

0.00301

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Ellis-van Creveld syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

3.0

PromoterAI

0.037

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Mutation Taster

=300/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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