4-5808197-C-G

Variant names:

• chr4-5808197-C-G
• rs60082311
• NM_153717.3:c.2562-4C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153717.3(EVC):​c.2562-4C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00463 in 1,554,030 control chromosomes in the GnomAD database, including 273 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (129 hom., cov: 27)
  • Exomes 𝑓: 0.0027 (144 hom.)
• Consequence: EVC NM_153717.3 splice_region, intron
• Scores: Splicing: ADA: 0.00001961
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0400
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 4-5808197-C-G is Benign according to our data. Variant chr4-5808197-C-G is described in ClinVar as Benign. ClinVar VariationId is 349206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 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.2562-4C>G		splice_region intron	N/A	NP_714928.1
	EVC	NM_001306090.2		c.2562-4C>G		splice_region intron	N/A	NP_001293019.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVC	ENST00000264956.11	TSL:1 MANE Select	c.2562-4C>G		splice_region intron	N/A	ENSP00000264956.6
	EVC	ENST00000861182.1		c.2562-4C>G		splice_region intron	N/A	ENSP00000531241.1
	EVC	ENST00000960562.1		c.2424-4C>G		splice_region intron	N/A	ENSP00000630621.1

Frequencies

GnomAD3 genomes AF: 0.0338 AC: 3305 AN: 97892 Hom.: 127 Cov.: 27

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0796

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.00367

Gnomad EAS AF: 0.000244

Gnomad SAS AF: 0.000327

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000623

Gnomad OTH AF: 0.0248

GnomAD2 exomes AF: 0.00627 AC: 1551 AN: 247556 AF XY: 0.00453

Gnomad AFR exome AF: 0.0831

Gnomad AMR exome AF: 0.00387

Gnomad ASJ exome AF: 0.00190

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000386

Gnomad OTH exome AF: 0.00396

GnomAD4 exome AF: 0.00265 AC: 3864 AN: 1456044 Hom.: 144 Cov.: 37 AF XY: 0.00238 AC XY: 1720 AN XY: 724166

African (AFR) AF: 0.0892 AC: 2949 AN: 33078

American (AMR) AF: 0.00463 AC: 206 AN: 44454

Ashkenazi Jewish (ASJ) AF: 0.00216 AC: 56 AN: 25946

East Asian (EAS) AF: 0.00 AC: 0 AN: 39560

South Asian (SAS) AF: 0.000407 AC: 35 AN: 85914

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52972

Middle Eastern (MID) AF: 0.00683 AC: 37 AN: 5416

European-Non Finnish (NFE) AF: 0.000133 AC: 148 AN: 1108708

Other (OTH) AF: 0.00722 AC: 433 AN: 59996

GnomAD4 genome AF: 0.0340 AC: 3328 AN: 97986 Hom.: 129 Cov.: 27 AF XY: 0.0333 AC XY: 1579 AN XY: 47352

African (AFR) AF: 0.113 AC: 3086 AN: 27420

American (AMR) AF: 0.0123 AC: 124 AN: 10044

Ashkenazi Jewish (ASJ) AF: 0.00367 AC: 9 AN: 2452

East Asian (EAS) AF: 0.000244 AC: 1 AN: 4096

South Asian (SAS) AF: 0.000328 AC: 1 AN: 3052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5508

Middle Eastern (MID) AF: 0.0208 AC: 4 AN: 192

European-Non Finnish (NFE) AF: 0.000623 AC: 27 AN: 43330

Other (OTH) AF: 0.0244 AC: 33 AN: 1352

Alfa AF: 0.00152 Hom.: 1

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Ellis-van Creveld syndrome (2)
-	-	2	not provided (2)
-	-	1	Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.55
DANN	Benign	0.60
PhyloP100		-0.040
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000020
dbscSNV1_RF	Benign	0.0
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: rs60082311; hg19: chr4-5809924;