chr4-5802102-AC-A

Variant names:

• chr4-5802102-AC-A
• rs398092136
• NM_153717.3:c.2449+15delC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_153717.3(EVC):​c.2449+15delC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7402 hom., cov: 20)
  • Exomes 𝑓: 0.34 (89767 hom.)
• Consequence: EVC NM_153717.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.121
• Publications: 1 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 -16 ACMG points.

• BP6: Variant 4-5802102-AC-A is Benign according to our data. Variant chr4-5802102-AC-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.525 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.2449+15delC		intron	N/A	NP_714928.1	P57679
	EVC	NM_001306090.2		c.2449+15delC		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.2449+9delC		intron	N/A	ENSP00000264956.6	P57679
	EVC	ENST00000861182.1		c.2449+9delC		intron	N/A	ENSP00000531241.1
	EVC	ENST00000960562.1		c.2311+9delC		intron	N/A	ENSP00000630621.1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44941 AN: 151864 Hom.: 7392 Cov.: 20

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.308

GnomAD2 exomes AF: 0.362 AC: 90872 AN: 251098 AF XY: 0.373

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.365

Gnomad ASJ exome AF: 0.311

Gnomad EAS exome AF: 0.516

Gnomad FIN exome AF: 0.323

Gnomad NFE exome AF: 0.332

Gnomad OTH exome AF: 0.346

GnomAD4 exome AF: 0.344 AC: 502670 AN: 1461582 Hom.: 89767 Cov.: 0 AF XY: 0.350 AC XY: 254657 AN XY: 727084

African (AFR) AF: 0.156 AC: 5211 AN: 33476

American (AMR) AF: 0.360 AC: 16097 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 7926 AN: 26134

East Asian (EAS) AF: 0.504 AC: 20003 AN: 39692

South Asian (SAS) AF: 0.526 AC: 45349 AN: 86242

European-Finnish (FIN) AF: 0.321 AC: 17163 AN: 53390

Middle Eastern (MID) AF: 0.338 AC: 1949 AN: 5766

European-Non Finnish (NFE) AF: 0.331 AC: 368297 AN: 1111788

Other (OTH) AF: 0.342 AC: 20675 AN: 60380

GnomAD4 genome AF: 0.296 AC: 44982 AN: 151982 Hom.: 7402 Cov.: 20 AF XY: 0.305 AC XY: 22648 AN XY: 74282

African (AFR) AF: 0.159 AC: 6596 AN: 41432

American (AMR) AF: 0.331 AC: 5050 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1062 AN: 3472

East Asian (EAS) AF: 0.515 AC: 2663 AN: 5168

South Asian (SAS) AF: 0.543 AC: 2613 AN: 4816

European-Finnish (FIN) AF: 0.320 AC: 3377 AN: 10552

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22484 AN: 67948

Other (OTH) AF: 0.306 AC: 646 AN: 2112

Alfa AF: 0.223 Hom.: 704

Bravo AF: 0.289

Asia WGS AF: 0.492 AC: 1708 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Ellis-van Creveld syndrome (3)
-	-	2	not provided (2)
-	-	1	Curry-Hall syndrome (1)
-	-	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
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs398092136; hg19: chr4-5803829; COSMIC: COSV99381333; COSMIC: COSV99381333;