4-5711401-C-G

Variant names:

• chr4-5711401-C-G
• rs1722983465
• NM_153717.3:c.21C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_153717.3(EVC):​c.21C>G​(p.Ala7Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EVC NM_153717.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.678
• 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]

EVC Gene-Disease associations (from GenCC):

• acrofacial dysostosis, Weyers type

  Inheritance: AD, Unknown, AR Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• Ellis-van Creveld syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 4-5711401-C-G is Benign according to our data. Variant chr4-5711401-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2022117.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.678 with no splicing effect.

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.21C>G	p.Ala7Ala	synonymous	Exon 1 of 21	NP_714928.1	P57679
	EVC	NM_001306090.2		c.21C>G	p.Ala7Ala	synonymous	Exon 1 of 21	NP_001293019.1
	EVC	NM_001306092.2		c.21C>G	p.Ala7Ala	synonymous	Exon 1 of 12	NP_001293021.1	E9PCN4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVC	ENST00000264956.11	TSL:1 MANE Select	c.21C>G	p.Ala7Ala	synonymous	Exon 1 of 21	ENSP00000264956.6	P57679
	EVC	ENST00000509451.1	TSL:1	c.21C>G	p.Ala7Ala	synonymous	Exon 1 of 12	ENSP00000426774.1	E9PCN4
	EVC	ENST00000861182.1		c.21C>G	p.Ala7Ala	synonymous	Exon 1 of 21	ENSP00000531241.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 871388 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 407928

African (AFR) AF: 0.00 AC: 0 AN: 16504

American (AMR) AF: 0.00 AC: 0 AN: 2426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6036

East Asian (EAS) AF: 0.00 AC: 0 AN: 5218

South Asian (SAS) AF: 0.00 AC: 0 AN: 17752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1796

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 788806

Other (OTH) AF: 0.00 AC: 0 AN: 29380

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	-0.67
CADD	Benign	13
DANN	Benign	0.90
PhyloP100		0.68
PromoterAI		-0.22	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs1722983465; hg19: chr4-5713128;