4-5748087-C-CCTTTG

Variant names:

• chr4-5748087-C-CCTTTG
• rs144810134
• NM_153717.3:c.940-61_940-60insCTTTG

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 36 AD,Unknown,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153717.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVC	NM_153717.3	MANE Select	c.940-61_940-60insCTTTG		intron	N/A	NP_714928.1	P57679
	EVC	NM_001306090.2		c.940-61_940-60insCTTTG		intron	N/A	NP_001293019.1
	EVC	NM_001306092.2		c.940-61_940-60insCTTTG		intron	N/A	NP_001293021.1	E9PCN4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVC	ENST00000264956.11	TSL:1 MANE Select	c.940-61_940-60insCTTTG		intron	N/A	ENSP00000264956.6	P57679
	EVC	ENST00000509451.1	TSL:1	c.940-61_940-60insCTTTG		intron	N/A	ENSP00000426774.1	E9PCN4
	EVC	ENST00000861182.1		c.940-61_940-60insCTTTG		intron	N/A	ENSP00000531241.1

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

African (AFR) AF: 0.0402 AC: 1314 AN: 32678

American (AMR) AF: 0.00294 AC: 131 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.000387 AC: 10 AN: 25860

East Asian (EAS) AF: 0.00 AC: 0 AN: 39472

South Asian (SAS) AF: 0.0000470 AC: 4 AN: 85076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52534

Middle Eastern (MID) AF: 0.00211 AC: 12 AN: 5682

European-Non Finnish (NFE) AF: 0.000256 AC: 277 AN: 1082128

Other (OTH) AF: 0.00318 AC: 188 AN: 59176

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

African (AFR) AF: 0.0393 AC: 1631 AN: 41468

American (AMR) AF: 0.00504 AC: 77 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68006

Other (OTH) AF: 0.00994 AC: 21 AN: 2112

Alfa AF: 0.0102 Hom.: 2

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs144810134; hg19: chr4-5749814;