chr4-5711469-C-G

Position:

• chr4-5711469-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153717.3(EVC):​c.89C>G​(p.Pro30Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,066,420 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P30L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000098 (0 hom.)
• Consequence: EVC NM_153717.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.795

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVC	NM_153717.3	c.89C>G	p.Pro30Arg	missense_variant	1/21	ENST00000264956.11	NP_714928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVC	ENST00000264956.11	c.89C>G	p.Pro30Arg	missense_variant	1/21	1	NM_153717.3	ENSP00000264956.6
EVC	ENST00000509451.1	c.89C>G	p.Pro30Arg	missense_variant	1/12	1		ENSP00000426774.1

Frequencies

GnomAD3 genomes AF: 0.0000135 AC: 2 AN: 147866 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000980 AC: 9 AN: 918554 Hom.: 0 Cov.: 30 AF XY: 0.00000925 AC XY: 4 AN XY: 432490

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000110

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000135 AC: 2 AN: 147866 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 71992

Gnomad4 AFR AF: 0.0000244

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000151

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.71	T;T
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.20
Sift	Uncertain	0.017	D;D
Sift4G	Uncertain	0.015	D;D
Polyphen		1.0	D;.
Vest4		0.54
MutPred		0.43		Gain of helix (P = 0.005);Gain of helix (P = 0.005);
MVP		0.63
ClinPred		0.58	D
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.11
gMVP		0.46

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

Other links and lift over

dbSNP: rs886044558; hg19: chr4-5713196;