rs565093715

Variant names:

• chr4-5793602-G-A
• rs565093715
• NM_153717.3:c.1777-6G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-5793602-G-A
• chr4-5793602-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_153717.3(EVC):​c.1777-6G>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 0.000261 in 1,551,386 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (4 hom.)
• Consequence: EVC NM_153717.3 splice_region, intron
• Scores: Splicing: ADA: 0.0009113
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.339
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-5793602-G-A is Benign according to our data. Variant chr4-5793602-G-A is described in ClinVar as Benign. ClinVar VariationId is 530947.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 AD,Unknown,AR gene

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.1777-6G>A		splice_region intron	N/A	NP_714928.1
	EVC	NM_001306090.2		c.1777-6G>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.1777-6G>A		splice_region intron	N/A	ENSP00000264956.6
	EVC	ENST00000861182.1		c.1777-6G>A		splice_region intron	N/A	ENSP00000531241.1
	EVC	ENST00000960562.1		c.1639-6G>A		splice_region intron	N/A	ENSP00000630621.1

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152236 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000718 AC: 112 AN: 155918 AF XY: 0.000986

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000272 AC: 380 AN: 1399032 Hom.: 4 Cov.: 29 AF XY: 0.000406 AC XY: 280 AN XY: 690086

African (AFR) AF: 0.00 AC: 0 AN: 31604

American (AMR) AF: 0.00 AC: 0 AN: 35740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35762

South Asian (SAS) AF: 0.00453 AC: 359 AN: 79224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5586

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078632

Other (OTH) AF: 0.000362 AC: 21 AN: 57988

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152354 Hom.: 0 Cov.: 32 AF XY: 0.000174 AC XY: 13 AN XY: 74500

African (AFR) AF: 0.00 AC: 0 AN: 41584

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00518 AC: 25 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000171 Hom.: 0

Bravo AF: 0.0000453

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.83
CADD	Benign	0.40
DANN	Benign	0.77
PhyloP100		-0.34
Mutation Taster		=40/60	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00091
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: rs565093715; hg19: chr4-5795329;