chr4-5731409-C-T

Variant names:

• chr4-5731409-C-T
• rs113571700
• NM_153717.3:c.385-16C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_153717.3(EVC):​c.385-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00626 in 1,599,726 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (22 hom., cov: 31)
  • Exomes 𝑓: 0.0058 (92 hom.)
• Consequence: EVC NM_153717.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0660
• 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]

EVC Gene-Disease associations (from GenCC):

• acrofacial dysostosis, Weyers type

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

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 4-5731409-C-T is Benign according to our data. Variant chr4-5731409-C-T is described in ClinVar as Benign. ClinVar VariationId is 262781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0104 (1582/151908) while in subpopulation SAS AF = 0.0308 (147/4772). AF 95% confidence interval is 0.0267. There are 22 homozygotes in GnomAd4. There are 805 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 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.385-16C>T		intron	N/A	NP_714928.1	P57679
	EVC	NM_001306090.2		c.385-16C>T		intron	N/A	NP_001293019.1
	EVC	NM_001306092.2		c.385-16C>T		intron	N/A	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.385-16C>T		intron	N/A	ENSP00000264956.6	P57679
	EVC	ENST00000509451.1	TSL:1	c.385-16C>T		intron	N/A	ENSP00000426774.1	E9PCN4
	EVC	ENST00000861182.1		c.385-16C>T		intron	N/A	ENSP00000531241.1

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1574 AN: 151790 Hom.: 22 Cov.: 31

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00551

Gnomad ASJ AF: 0.00894

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0308

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00390

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00821 AC: 2045 AN: 249028 AF XY: 0.00931

Gnomad AFR exome AF: 0.0249

Gnomad AMR exome AF: 0.00385

Gnomad ASJ exome AF: 0.0127

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00450

Gnomad OTH exome AF: 0.00655

GnomAD4 exome AF: 0.00582 AC: 8425 AN: 1447818 Hom.: 92 Cov.: 30 AF XY: 0.00654 AC XY: 4715 AN XY: 721288

African (AFR) AF: 0.0287 AC: 951 AN: 33170

American (AMR) AF: 0.00398 AC: 178 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 291 AN: 26018

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39606

South Asian (SAS) AF: 0.0282 AC: 2421 AN: 85970

European-Finnish (FIN) AF: 0.000487 AC: 26 AN: 53368

Middle Eastern (MID) AF: 0.0218 AC: 125 AN: 5746

European-Non Finnish (NFE) AF: 0.00357 AC: 3922 AN: 1099328

Other (OTH) AF: 0.00843 AC: 505 AN: 59898

GnomAD4 genome AF: 0.0104 AC: 1582 AN: 151908 Hom.: 22 Cov.: 31 AF XY: 0.0108 AC XY: 805 AN XY: 74224

African (AFR) AF: 0.0247 AC: 1022 AN: 41430

American (AMR) AF: 0.00550 AC: 84 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00894 AC: 31 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5156

South Asian (SAS) AF: 0.0308 AC: 147 AN: 4772

European-Finnish (FIN) AF: 0.0000946 AC: 1 AN: 10574

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00390 AC: 265 AN: 67936

Other (OTH) AF: 0.0119 AC: 25 AN: 2108

Alfa AF: 0.00829 Hom.: 1

Bravo AF: 0.0111

Asia WGS AF: 0.0170 AC: 58 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Ellis-van Creveld syndrome (1)
-	-	1	Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.82
DANN	Benign	0.36
PhyloP100		-0.066
Mutation Taster		=100/0	polymorphism

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: rs113571700; hg19: chr4-5733136;