rs6826372

Positions:

• chr4-5793177-A-G

Variant summary

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

The NM_153717.3(EVC):​c.1777-431A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,128 control chromosomes in the GnomAD database, including 2,787 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 0.18 (2787 hom., cov: 32)
• Consequence: EVC NM_153717.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455

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]

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]

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 = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EVC	NM_153717.3	c.1777-431A>G		intron_variant		ENST00000264956.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVC	ENST00000264956.11	c.1777-431A>G		intron_variant		1	NM_153717.3	P1
CRMP1	ENST00000506216.5	n.1647+32317T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27853 AN: 152010 Hom.: 2785 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.0902

Gnomad EAS AF: 0.0342

Gnomad SAS AF: 0.0818

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.183 AC: 27861 AN: 152128 Hom.: 2787 Cov.: 32 AF XY: 0.180 AC XY: 13372 AN XY: 74382

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.0902

Gnomad4 EAS AF: 0.0337

Gnomad4 SAS AF: 0.0815

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.150

Alfa AF: 0.176 Hom.: 2869

Bravo AF: 0.181

Asia WGS AF: 0.0710 AC: 249 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	3.2
DANN	Benign	0.51

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: rs6826372; hg19: chr4-5794904;