chr4-5748087-C-CGTTTG

Variant names:

• chr4-5748087-C-CGTTTG
• rs58769270
• NM_153717.3:c.940-59_940-55dupTTTGG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_153717.3(EVC):​c.940-59_940-55dupTTTGG 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
• Publications: 2 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-CGTTTG is Benign according to our data. Variant chr4-5748087-C-CGTTTG is described in ClinVar as Benign. ClinVar VariationId 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.

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.940-59_940-55dupTTTGG		intron	N/A	NP_714928.1	P57679
	EVC	NM_001306090.2		c.940-59_940-55dupTTTGG		intron	N/A	NP_001293019.1
	EVC	NM_001306092.2		c.940-59_940-55dupTTTGG		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.940-59_940-55dupTTTGG		intron	N/A	ENSP00000264956.6	P57679
	EVC	ENST00000509451.1	TSL:1	c.940-59_940-55dupTTTGG		intron	N/A	ENSP00000426774.1	E9PCN4
	EVC	ENST00000861182.1		c.940-59_940-55dupTTTGG		intron	N/A	ENSP00000531241.1

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

African (AFR) AF: 0.216 AC: 7049 AN: 32650

American (AMR) AF: 0.0452 AC: 2012 AN: 44548

Ashkenazi Jewish (ASJ) AF: 0.0684 AC: 1768 AN: 25860

East Asian (EAS) AF: 0.000329 AC: 13 AN: 39472

South Asian (SAS) AF: 0.0456 AC: 3878 AN: 85070

European-Finnish (FIN) AF: 0.0679 AC: 3566 AN: 52514

Middle Eastern (MID) AF: 0.0808 AC: 459 AN: 5682

European-Non Finnish (NFE) AF: 0.0689 AC: 74508 AN: 1081584

Other (OTH) AF: 0.0743 AC: 4392 AN: 59150

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

African (AFR) AF: 0.210 AC: 8694 AN: 41442

American (AMR) AF: 0.0652 AC: 996 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0703 AC: 244 AN: 3470

East Asian (EAS) AF: 0.000583 AC: 3 AN: 5144

South Asian (SAS) AF: 0.0418 AC: 201 AN: 4812

European-Finnish (FIN) AF: 0.0715 AC: 757 AN: 10592

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0668 AC: 4544 AN: 68004

Other (OTH) AF: 0.109 AC: 229 AN: 2110

Alfa AF: 0.0935 Hom.: 99

ClinVar

ClinVar submissions

Significance: 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 (auto)

Splicing

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

Other links and lift over

dbSNP: rs58769270; hg19: chr4-5749814;