rs60082311

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-5808197-C-A
• chr4-5808197-C-G
• chr4-5808197-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_153717.3(EVC):​c.2562-4C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000965 in 1,554,026 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: EVC NM_153717.3 splice_region, intron
• Scores: Splicing: ADA: 0.00001961
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 4-5808197-C-A is Benign according to our data. Variant chr4-5808197-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 772719.Status of the report is criteria_provided_single_submitter, 1 stars.

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>A		splice_region intron	N/A	NP_714928.1
	EVC	NM_001306090.2		c.2562-4C>A		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>A		splice_region intron	N/A	ENSP00000264956.6
	EVC	ENST00000861182.1		c.2562-4C>A		splice_region intron	N/A	ENSP00000531241.1
	EVC	ENST00000960562.1		c.2424-4C>A		splice_region intron	N/A	ENSP00000630621.1

Frequencies

GnomAD3 genomes AF: 0.0000204 AC: 2 AN: 97980 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000996

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000751

GnomAD2 exomes AF: 0.0000242 AC: 6 AN: 247556 AF XY: 0.0000299

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000874

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.00000893 AC: 13 AN: 1456046 Hom.: 0 Cov.: 37 AF XY: 0.00000690 AC XY: 5 AN XY: 724168

African (AFR) AF: 0.0000302 AC: 1 AN: 33080

American (AMR) AF: 0.000157 AC: 7 AN: 44454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25946

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85914

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5416

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108708

Other (OTH) AF: 0.0000333 AC: 2 AN: 59996

GnomAD4 genome AF: 0.0000204 AC: 2 AN: 97980 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 47286

African (AFR) AF: 0.00 AC: 0 AN: 27410

American (AMR) AF: 0.0000996 AC: 1 AN: 10036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2452

East Asian (EAS) AF: 0.00 AC: 0 AN: 4104

South Asian (SAS) AF: 0.00 AC: 0 AN: 3056

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 210

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 43332

Other (OTH) AF: 0.000751 AC: 1 AN: 1332

Alfa AF: 0.00 Hom.: 1

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.45
DANN	Benign	0.68
PhyloP100		-0.040
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000020
dbscSNV1_RF	Benign	0.0040
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;