rs10937678

chr4-5795761-C-Achr4-5795761-C-T

Variant summary

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

The NM_153717.3(EVC):c.1887-1261C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,154 control chromosomes in the GnomAD database, including 7,339 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 0.29 (7339 hom., cov: 32)
• Consequence: EVC NM_153717.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EVC	NM_153717.3	c.1887-1261C>A		intron_variant		ENST00000264956.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVC	ENST00000264956.11	c.1887-1261C>A		intron_variant		1	NM_153717.3	P1
CRMP1	ENST00000506216.5	n.1647+29733G>T		intron_variant, non_coding_transcript_variant		5
EVC	ENST00000506240.1	n.205-1261C>A		intron_variant, non_coding_transcript_variant		3
EVC	ENST00000515113.1	n.111-1261C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44772 AN: 152036 Hom.: 7333 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.294 AC: 44799 AN: 152154 Hom.: 7339 Cov.: 32 AF XY: 0.303 AC XY: 22576 AN XY: 74408

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.302

Alfa AF: 0.243 Hom.: 1043

Bravo AF: 0.289

Asia WGS AF: 0.488 AC: 1693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.80
Dann	Benign	0.45

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: rs10937678; hg19: chr4-5797488;