chr4-5745351-A-G

Variant names:

• chr4-5745351-A-G
• rs2286342
• NM_153717.3:c.939+10A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153717.3(EVC):​c.939+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 1,613,168 control chromosomes in the GnomAD database, including 362,604 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (33943 hom., cov: 30)
  • Exomes 𝑓: 0.67 (328661 hom.)
• Consequence: EVC NM_153717.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.191
• Publications: 10 publications found

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: AR, Unknown, AD Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• Ellis-van Creveld syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 4-5745351-A-G is Benign according to our data. Variant chr4-5745351-A-G is described in ClinVar as Benign. ClinVar VariationId is 262784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVC	NM_153717.3	MANE Select	c.939+10A>G		intron	N/A	NP_714928.1	P57679
	EVC	NM_001306090.2		c.939+10A>G		intron	N/A	NP_001293019.1
	EVC	NM_001306092.2		c.939+10A>G		intron	N/A	NP_001293021.1	E9PCN4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVC	ENST00000264956.11	TSL:1 MANE Select	c.939+10A>G		intron	N/A	ENSP00000264956.6	P57679
	EVC	ENST00000509451.1	TSL:1	c.939+10A>G		intron	N/A	ENSP00000426774.1	E9PCN4
	EVC	ENST00000861182.1		c.939+10A>G		intron	N/A	ENSP00000531241.1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100741 AN: 151844 Hom.: 33920 Cov.: 30

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.657

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.656

GnomAD2 exomes AF: 0.621 AC: 156079 AN: 251244 AF XY: 0.624

Gnomad AFR exome AF: 0.712

Gnomad AMR exome AF: 0.479

Gnomad ASJ exome AF: 0.699

Gnomad EAS exome AF: 0.351

Gnomad FIN exome AF: 0.677

Gnomad NFE exome AF: 0.684

Gnomad OTH exome AF: 0.646

GnomAD4 exome AF: 0.667 AC: 973956 AN: 1461206 Hom.: 328661 Cov.: 41 AF XY: 0.664 AC XY: 482989 AN XY: 726946

African (AFR) AF: 0.713 AC: 23850 AN: 33470

American (AMR) AF: 0.491 AC: 21950 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 18382 AN: 26122

East Asian (EAS) AF: 0.338 AC: 13414 AN: 39680

South Asian (SAS) AF: 0.594 AC: 51252 AN: 86242

European-Finnish (FIN) AF: 0.673 AC: 35911 AN: 53378

Middle Eastern (MID) AF: 0.625 AC: 3603 AN: 5768

European-Non Finnish (NFE) AF: 0.689 AC: 765609 AN: 1111492

Other (OTH) AF: 0.663 AC: 39985 AN: 60352

GnomAD4 genome AF: 0.664 AC: 100830 AN: 151962 Hom.: 33943 Cov.: 30 AF XY: 0.657 AC XY: 48843 AN XY: 74292

African (AFR) AF: 0.713 AC: 29542 AN: 41424

American (AMR) AF: 0.568 AC: 8690 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 2441 AN: 3468

East Asian (EAS) AF: 0.351 AC: 1808 AN: 5152

South Asian (SAS) AF: 0.590 AC: 2832 AN: 4802

European-Finnish (FIN) AF: 0.680 AC: 7175 AN: 10558

Middle Eastern (MID) AF: 0.666 AC: 193 AN: 290

European-Non Finnish (NFE) AF: 0.680 AC: 46213 AN: 67960

Other (OTH) AF: 0.656 AC: 1384 AN: 2110

Alfa AF: 0.688 Hom.: 10643

Bravo AF: 0.656

Asia WGS AF: 0.490 AC: 1708 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Ellis-van Creveld syndrome (4)
-	-	3	not specified (3)
-	-	1	Curry-Hall syndrome (1)
-	-	1	Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.1
DANN	Benign	0.53
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2286342; hg19: chr4-5747078; COSMIC: COSV53830462; COSMIC: COSV53830462;