rs11939527

Positions:

• chr4-5759639-G-A
• chr4-5759639-G-T

Variant summary

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

The NM_153717.3(EVC):​c.1563+3277G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,078 control chromosomes in the GnomAD database, including 5,608 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 0.27 (5608 hom., cov: 33)
• Consequence: EVC NM_153717.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EVC	NM_153717.3	c.1563+3277G>A		intron_variant		ENST00000264956.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVC	ENST00000264956.11	c.1563+3277G>A		intron_variant		1	NM_153717.3	P1
CRMP1	ENST00000506216.5	n.1648-11327C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40471 AN: 151960 Hom.: 5603 Cov.: 33

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.266 AC: 40500 AN: 152078 Hom.: 5608 Cov.: 33 AF XY: 0.270 AC XY: 20044 AN XY: 74350

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.269

Alfa AF: 0.249 Hom.: 10094

Bravo AF: 0.263

Asia WGS AF: 0.424 AC: 1474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.70
DANN	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11939527; hg19: chr4-5761366;