chr4-5539923-C-T

Variant names:

• chr4-5539923-C-T
• rs12505562
• XR_007058006.1:n.9173G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007058006.1(LOC124900166):​n.9173G>A variant causes a non coding transcript exon 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: LOC124900166 XR_007058006.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.841
• Publications: 4 publications found

Genes affected

LOC124900166 (HGNC:):

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]

EVC2 Gene-Disease associations (from GenCC):

• acrofacial dysostosis, Weyers type

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

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

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

African (AFR) AF: 0.296 AC: 12246 AN: 41426

American (AMR) AF: 0.118 AC: 1803 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3466

East Asian (EAS) AF: 0.234 AC: 1209 AN: 5176

South Asian (SAS) AF: 0.288 AC: 1386 AN: 4820

European-Finnish (FIN) AF: 0.148 AC: 1559 AN: 10562

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7208 AN: 67992

Other (OTH) AF: 0.172 AC: 363 AN: 2110

Alfa AF: 0.126 Hom.: 5636

Bravo AF: 0.170

Asia WGS AF: 0.320 AC: 1111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.020
DANN	Benign	0.43
PhyloP100		-0.84

Splicing

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

Other links and lift over

dbSNP: rs12505562; hg19: chr4-5541650;