4-5748087-C-CCTTTG

Position:

• chr4-5748087-C-CCTTTG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_153717.3(EVC):​c.940-61_940-60insCTTTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,579,252 control chromosomes in the GnomAD database, including 75 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (36 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (39 hom.)
• Consequence: EVC NM_153717.3 intron
• Clinical Significance: Likely 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-CCTTTG is Benign according to our data. Variant chr4-5748087-C-CCTTTG is described in ClinVar as [Likely_benign]. Clinvar id is 1186208.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1750/152096) while in subpopulation AFR AF= 0.0393 (1631/41468). AF 95% confidence interval is 0.0377. There are 36 homozygotes in gnomad4. There are 821 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EVC	NM_153717.3	c.940-61_940-60insCTTTG		intron_variant		ENST00000264956.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVC	ENST00000264956.11	c.940-61_940-60insCTTTG		intron_variant		1	NM_153717.3	P1
EVC	ENST00000509451.1	c.940-61_940-60insCTTTG		intron_variant		1
CRMP1	ENST00000506216.5	n.1872_1873insCAAAG		non_coding_transcript_exon_variant	13/13	5

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1750 AN: 151978 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.0394

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0100

GnomAD4 exome AF: 0.00136 AC: 1936 AN: 1427156 Hom.: 39 Cov.: 28 AF XY: 0.00115 AC XY: 817 AN XY: 712350

Gnomad4 AFR exome AF: 0.0402

Gnomad4 AMR exome AF: 0.00294

Gnomad4 ASJ exome AF: 0.000387

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000470

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000256

Gnomad4 OTH exome AF: 0.00318

GnomAD4 genome AF: 0.0115 AC: 1750 AN: 152096 Hom.: 36 Cov.: 32 AF XY: 0.0110 AC XY: 821 AN XY: 74344

Gnomad4 AFR AF: 0.0393

Gnomad4 AMR AF: 0.00504

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.0102 Hom.: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 20, 2019

- -

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: rs144810134; hg19: chr4-5749814;