rs2306400

Variant names:

• chr4-5801906-C-T
• rs2306400
• NM_153717.3:c.2305-44C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-5801906-C-T
• chr4-5801906-C-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.2305-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,603,566 control chromosomes in the GnomAD database, including 95,310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (7063 hom., cov: 33)
  • Exomes 𝑓: 0.34 (88247 hom.)
• Consequence: EVC NM_153717.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.15
• Publications: 8 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 4-5801906-C-T is Benign according to our data. Variant chr4-5801906-C-T is described in ClinVar as Benign. ClinVar VariationId is 262773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.519 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.2305-44C>T		intron	N/A	NP_714928.1	P57679
	EVC	NM_001306090.2		c.2305-44C>T		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.2305-44C>T		intron	N/A	ENSP00000264956.6	P57679
	EVC	ENST00000861182.1		c.2305-44C>T		intron	N/A	ENSP00000531241.1
	EVC	ENST00000960562.1		c.2167-44C>T		intron	N/A	ENSP00000630621.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42547 AN: 152064 Hom.: 7056 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.294

GnomAD2 exomes AF: 0.357 AC: 85139 AN: 238712 AF XY: 0.369

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.360

Gnomad ASJ exome AF: 0.310

Gnomad EAS exome AF: 0.515

Gnomad FIN exome AF: 0.321

Gnomad NFE exome AF: 0.330

Gnomad OTH exome AF: 0.343

GnomAD4 exome AF: 0.342 AC: 495986 AN: 1451382 Hom.: 88247 Cov.: 30 AF XY: 0.348 AC XY: 251111 AN XY: 721344

African (AFR) AF: 0.100 AC: 3341 AN: 33334

American (AMR) AF: 0.355 AC: 15425 AN: 43482

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 7790 AN: 25918

East Asian (EAS) AF: 0.504 AC: 19890 AN: 39488

South Asian (SAS) AF: 0.522 AC: 44321 AN: 84876

European-Finnish (FIN) AF: 0.321 AC: 16954 AN: 52780

Middle Eastern (MID) AF: 0.341 AC: 1457 AN: 4268

European-Non Finnish (NFE) AF: 0.331 AC: 366551 AN: 1107322

Other (OTH) AF: 0.338 AC: 20257 AN: 59914

GnomAD4 genome AF: 0.280 AC: 42575 AN: 152184 Hom.: 7063 Cov.: 33 AF XY: 0.289 AC XY: 21490 AN XY: 74386

African (AFR) AF: 0.105 AC: 4358 AN: 41560

American (AMR) AF: 0.325 AC: 4962 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1049 AN: 3470

East Asian (EAS) AF: 0.514 AC: 2656 AN: 5168

South Asian (SAS) AF: 0.537 AC: 2591 AN: 4828

European-Finnish (FIN) AF: 0.320 AC: 3383 AN: 10588

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22473 AN: 67984

Other (OTH) AF: 0.292 AC: 615 AN: 2106

Alfa AF: 0.234 Hom.: 904

Bravo AF: 0.272

Asia WGS AF: 0.483 AC: 1678 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.79
PhyloP100		-1.2
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

Other links and lift over

dbSNP: rs2306400; hg19: chr4-5803633; COSMIC: COSV53837157; COSMIC: COSV53837157;