4-5757142-T-C

Variant names:

• chr4-5757142-T-C
• rs735172
• NM_153717.3:c.1563+780T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153717.3(EVC):​c.1563+780T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,066 control chromosomes in the GnomAD database, including 7,143 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 0.30 (7143 hom., cov: 32)
• Consequence: EVC NM_153717.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• Publications: 15 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.307 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.1563+780T>C		intron	N/A	NP_714928.1	P57679
	EVC	NM_001306090.2		c.1563+780T>C		intron	N/A	NP_001293019.1
	EVC	NM_001306092.2		c.1563+780T>C		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.1563+780T>C		intron	N/A	ENSP00000264956.6	P57679
	EVC	ENST00000509451.1	TSL:1	c.1563+780T>C		intron	N/A	ENSP00000426774.1	E9PCN4
	EVC	ENST00000861182.1		c.1563+780T>C		intron	N/A	ENSP00000531241.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46055 AN: 151948 Hom.: 7137 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.303 AC: 46098 AN: 152066 Hom.: 7143 Cov.: 32 AF XY: 0.305 AC XY: 22677 AN XY: 74324

African (AFR) AF: 0.296 AC: 12266 AN: 41494

American (AMR) AF: 0.298 AC: 4556 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 889 AN: 3470

East Asian (EAS) AF: 0.183 AC: 943 AN: 5164

South Asian (SAS) AF: 0.318 AC: 1530 AN: 4814

European-Finnish (FIN) AF: 0.356 AC: 3765 AN: 10568

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21131 AN: 67970

Other (OTH) AF: 0.287 AC: 607 AN: 2114

Alfa AF: 0.304 Hom.: 30150

Bravo AF: 0.298

Asia WGS AF: 0.272 AC: 942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.045
DANN	Benign	0.44
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs735172; hg19: chr4-5758869; COSMIC: COSV53829478;