chr4-5539923-C-T

Position:

• chr4-5539923-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047449611.1(EVC2):​c.3420-5113G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,032 control chromosomes in the GnomAD database, including 2,741 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2741 hom., cov: 33)
• Consequence: EVC2 XM_047449611.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.841

Genes affected

EVC2 (HGNC:19747): (EvC ciliary complex subunit 2) This gene encodes a protein that functions in bone formation and skeletal development. Mutations in this gene, as well as in a neighboring gene that lies in a head-to-head configuration, cause Ellis-van Creveld syndrome, an autosomal recessive skeletal dysplasia that is also known as chondroectodermal dysplasia. Mutations in this gene also cause acrofacial dysostosis Weyers type, also referred to as Curry-Hall syndrome, a disease that combines limb and facial abnormalities. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

LOC124900166 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVC2	XM_047449611.1	c.3420-5113G>A		intron_variant			XP_047305567.1
LOC124900166	XR_007058006.1	n.9173G>A		non_coding_transcript_exon_variant	2/2
		n.5539923C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26169 AN: 151914 Hom.: 2715 Cov.: 33

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.161

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.173 AC: 26238 AN: 152032 Hom.: 2741 Cov.: 33 AF XY: 0.176 AC XY: 13064 AN XY: 74322

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.172

Alfa AF: 0.117 Hom.: 2063

Bravo AF: 0.170

Asia WGS AF: 0.320 AC: 1111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.020
DANN	Benign	0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12505562; hg19: chr4-5541650;