Genetic Variant NM_153717.3:c.940-61C>T (chr4-5748087-C-T) – 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.940-61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,578,494 control chromosomes in the GnomAD database, including 17,709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1946 hom., cov: 34)

Exomes 𝑓: 0.13 ( 15763 hom. )

Consequence

EVC
NM_153717.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.440

Publications

7 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=-0.8).

BP6

Variant 4-5748087-C-T is Benign according to our data. Variant chr4-5748087-C-T is described in ClinVar as Benign. ClinVar VariationId is 1266411.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 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.940-61C>T	intron	N/A	NP_714928.1	P57679
EVC	NM_001306090.2		c.940-61C>T	intron	N/A	NP_001293019.1
EVC	NM_001306092.2		c.940-61C>T	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.940-61C>T	intron	N/A	ENSP00000264956.6	P57679
EVC	ENST00000509451.1	TSL:1	c.940-61C>T	intron	N/A	ENSP00000426774.1	E9PCN4
EVC	ENST00000861182.1		c.940-61C>T	intron	N/A	ENSP00000531241.1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22306

AN:

151960

Hom.:

1946

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.177

Gnomad EAS

AF:

0.429

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.100

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.161

GnomAD4 exome

AF:

0.130

AC:

185404

AN:

1426416

Hom.:

15763

Cov.:

AF XY:

0.133

AC XY:

94581

AN XY:

712020

show subpopulations

African (AFR)

AF:

0.153

AC:

5010

AN:

32678

American (AMR)

AF:

0.237

AC:

10543

AN:

44540

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

4559

AN:

25842

East Asian (EAS)

AF:

0.440

AC:

17370

AN:

39442

South Asian (SAS)

AF:

0.224

AC:

19080

AN:

85040

European-Finnish (FIN)

AF:

0.0949

AC:

4985

AN:

52516

Middle Eastern (MID)

AF:

0.185

AC:

1048

AN:

5676

European-Non Finnish (NFE)

AF:

0.106

AC:

114133

AN:

1081544

Other (OTH)

AF:

0.147

AC:

8676

AN:

59138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

7887

15773

23660

31546

39433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4436

8872

13308

17744

22180

<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:

0.147

AC:

22320

AN:

152078

Hom.:

1946

Cov.:

AF XY:

0.151

AC XY:

11236

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.153

AC:

6348

AN:

41464

American (AMR)

AF:

0.200

AC:

3054

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

613

AN:

3470

East Asian (EAS)

AF:

0.430

AC:

2210

AN:

5140

South Asian (SAS)

AF:

0.230

AC:

1109

AN:

4814

European-Finnish (FIN)

AF:

0.100

AC:

1061

AN:

10588

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7374

AN:

68004

Other (OTH)

AF:

0.163

AC:

343

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

996

1992

2989

3985

4981

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

254

508

762

1016

1270

<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:

0.123

Hom.:

1697

Bravo

AF:

0.158

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.8

(source)

DANN

Benign

0.75

PhyloP100

-0.44

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

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