rs1031919

Variant names:

• chr4-5801942-T-C
• rs1031919
• NM_153717.3:c.2305-8T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-5801942-T-C
• chr4-5801942-T-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.2305-8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,612,074 control chromosomes in the GnomAD database, including 432,017 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 0.72 (39628 hom., cov: 33)
  • Exomes 𝑓: 0.73 (392389 hom.)
• Consequence: EVC NM_153717.3 splice_region, intron
• Scores: Splicing: ADA: 0.00005523
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -1.05
• Publications: 13 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=-0.9).
• BP6: Variant 4-5801942-T-C is Benign according to our data. Variant chr4-5801942-T-C is described in ClinVar as Benign. ClinVar VariationId is 262774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.79 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.2305-8T>C		splice_region intron	N/A	NP_714928.1	P57679
	EVC	NM_001306090.2		c.2305-8T>C		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.2305-8T>C		splice_region intron	N/A	ENSP00000264956.6	P57679
	EVC	ENST00000861182.1		c.2305-8T>C		splice_region intron	N/A	ENSP00000531241.1
	EVC	ENST00000960562.1		c.2167-8T>C		splice_region intron	N/A	ENSP00000630621.1

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109631 AN: 152034 Hom.: 39592 Cov.: 33

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.704

GnomAD2 exomes AF: 0.719 AC: 179567 AN: 249798 AF XY: 0.727

Gnomad AFR exome AF: 0.716

Gnomad AMR exome AF: 0.644

Gnomad ASJ exome AF: 0.685

Gnomad EAS exome AF: 0.549

Gnomad FIN exome AF: 0.783

Gnomad NFE exome AF: 0.733

Gnomad OTH exome AF: 0.715

GnomAD4 exome AF: 0.732 AC: 1068320 AN: 1459922 Hom.: 392389 Cov.: 53 AF XY: 0.734 AC XY: 533351 AN XY: 726242

African (AFR) AF: 0.708 AC: 23682 AN: 33438

American (AMR) AF: 0.650 AC: 28970 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 17807 AN: 26114

East Asian (EAS) AF: 0.537 AC: 21306 AN: 39682

South Asian (SAS) AF: 0.819 AC: 70540 AN: 86132

European-Finnish (FIN) AF: 0.776 AC: 41395 AN: 53368

Middle Eastern (MID) AF: 0.699 AC: 3418 AN: 4890

European-Non Finnish (NFE) AF: 0.736 AC: 818123 AN: 1111474

Other (OTH) AF: 0.715 AC: 43079 AN: 60254

GnomAD4 genome AF: 0.721 AC: 109717 AN: 152152 Hom.: 39628 Cov.: 33 AF XY: 0.724 AC XY: 53850 AN XY: 74406

African (AFR) AF: 0.709 AC: 29404 AN: 41486

American (AMR) AF: 0.685 AC: 10481 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2333 AN: 3472

East Asian (EAS) AF: 0.552 AC: 2844 AN: 5152

South Asian (SAS) AF: 0.811 AC: 3912 AN: 4824

European-Finnish (FIN) AF: 0.788 AC: 8358 AN: 10606

Middle Eastern (MID) AF: 0.668 AC: 195 AN: 292

European-Non Finnish (NFE) AF: 0.734 AC: 49944 AN: 68000

Other (OTH) AF: 0.698 AC: 1476 AN: 2114

Alfa AF: 0.728 Hom.: 17451

Bravo AF: 0.708

Asia WGS AF: 0.678 AC: 2358 AN: 3478

EpiCase AF: 0.718

EpiControl AF: 0.722

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Ellis-van Creveld syndrome (3)
-	-	1	Curry-Hall syndrome (1)
-	-	1	Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.61
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000055
dbscSNV1_RF	Benign	0.0020
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: rs1031919; hg19: chr4-5803669; COSMIC: COSV53830478; COSMIC: COSV53830478;