4-5748087-C-CGTTTG

Position:

• chr4-5748087-C-CGTTTG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_153717.3(EVC):​c.940-59_940-55dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0718 in 1,578,592 control chromosomes in the GnomAD database, including 5,218 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1150 hom., cov: 32)
  • Exomes 𝑓: 0.068 (4068 hom.)
• Consequence: EVC NM_153717.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.00

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 -10 ACMG points.

• BP6: Variant 4-5748087-C-CGTTTG is Benign according to our data. Variant chr4-5748087-C-CGTTTG is described in ClinVar as [Benign]. Clinvar id is 1231697.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EVC	NM_153717.3	c.940-59_940-55dup		intron_variant		ENST00000264956.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVC	ENST00000264956.11	c.940-59_940-55dup		intron_variant		1	NM_153717.3	P1
EVC	ENST00000509451.1	c.940-59_940-55dup		intron_variant		1
CRMP1	ENST00000506216.5	n.1872_1873insCAAAC		non_coding_transcript_exon_variant	13/13	5

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15754 AN: 151944 Hom.: 1150 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.0654

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.000582

Gnomad SAS AF: 0.0426

Gnomad FIN AF: 0.0715

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.110

GnomAD4 exome AF: 0.0684 AC: 97645 AN: 1426530 Hom.: 4068 Cov.: 28 AF XY: 0.0674 AC XY: 48001 AN XY: 712074

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.0452

Gnomad4 ASJ exome AF: 0.0684

Gnomad4 EAS exome AF: 0.000329

Gnomad4 SAS exome AF: 0.0456

Gnomad4 FIN exome AF: 0.0679

Gnomad4 NFE exome AF: 0.0689

Gnomad4 OTH exome AF: 0.0743

GnomAD4 genome AF: 0.104 AC: 15766 AN: 152062 Hom.: 1150 Cov.: 32 AF XY: 0.102 AC XY: 7563 AN XY: 74330

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.0652

Gnomad4 ASJ AF: 0.0703

Gnomad4 EAS AF: 0.000583

Gnomad4 SAS AF: 0.0418

Gnomad4 FIN AF: 0.0715

Gnomad4 NFE AF: 0.0668

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0935 Hom.: 99

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 17, 2020

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58769270; hg19: chr4-5749814;