3-14124780-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001098502.2(CHCHD4):c.-104G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,301,642 control chromosomes in the GnomAD database, including 8,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.087 ( 809 hom., cov: 32)

Exomes 𝑓: 0.11 ( 7208 hom. )

Consequence

CHCHD4
NM_001098502.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.191

Variant links:

Genes affected

CHCHD4 (HGNC:26467): (coiled-coil-helix-coiled-coil-helix domain containing 4) CHCHD4, a component of human mitochondria, belongs to a protein family whose members share 6 highly conserved cysteine residues constituting a -CXC-CX(9)C-CX(9)C- motif in the C terminus (Hofmann et al., 2005 [PubMed 16185709]).[supplied by OMIM, Mar 2008]

CHCHD4 links:

TMEM43 (HGNC:28472): (transmembrane protein 43) This gene belongs to the TMEM43 family. Defects in this gene are the cause of familial arrhythmogenic right ventricular dysplasia type 5 (ARVD5), also known as arrhythmogenic right ventricular cardiomyopathy type 5 (ARVC5). Arrhythmogenic right ventricular dysplasia is an inherited disorder, often involving both ventricles, and is characterized by ventricular tachycardia, heart failure, sudden cardiac death, and fibrofatty replacement of cardiomyocytes. This gene contains a response element for PPAR gamma (an adipogenic transcription factor), which may explain the fibrofatty replacement of the myocardium, a characteristic pathological finding in ARVC. [provided by RefSeq, Oct 2008]

TMEM43 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 3-14124780-C-T is Benign according to our data. Variant chr3-14124780-C-T is described in ClinVar as [Benign]. Clinvar id is 684005.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHCHD4	NM_001098502.2 link	c.-104G>A		5_prime_UTR_variant	Exon 1 of 3	ENST00000396914.4	NP_001091972.1	Q8N4Q1-1A0A024R2I5
CHCHD4	NM_144636.3 link	c.-235G>A		5_prime_UTR_variant	Exon 1 of 4		NP_653237.1	Q8N4Q1-2A0A024R2F8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHCHD4	ENST00000396914.4 link	c.-104G>A	5_prime_UTR_variant	Exon 1 of 3	1	NM_001098502.2	ENSP00000380122.3	Q8N4Q1-1
CHCHD4	ENST00000295767.9 link	c.-235G>A	5_prime_UTR_variant	Exon 1 of 4	2		ENSP00000295767.5	Q8N4Q1-2
CHCHD4	ENST00000420103.1 link	n.-31G>A	upstream_gene_variant		3
TMEM43	ENST00000432444.2 link	n.-414C>T	upstream_gene_variant		3		ENSP00000395617.1	F8WDL3

Frequencies

GnomAD3 genomes

AF:

0.0873

AC:

13266

AN:

152038

Hom.:

809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0231

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0881

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.0519

Gnomad FIN

AF:

0.213

Gnomad MID

AF:

0.0828

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.113

GnomAD4 exome

AF:

0.108

AC:

123636

AN:

1149496

Hom.:

7208

Cov.:

AF XY:

0.106

AC XY:

60322

AN XY:

566646

show subpopulations

Gnomad4 AFR exome

AF:

0.0214

Gnomad4 AMR exome

AF:

0.0773

Gnomad4 ASJ exome

AF:

0.122

Gnomad4 EAS exome

AF:

0.000257

Gnomad4 SAS exome

AF:

0.0586

Gnomad4 FIN exome

AF:

0.203

Gnomad4 NFE exome

AF:

0.114

Gnomad4 OTH exome

AF:

0.0968

GnomAD4 genome

AF:

0.0872

AC:

13263

AN:

152146

Hom.:

809

Cov.:

AF XY:

0.0915

AC XY:

6809

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0231

Gnomad4 AMR

AF:

0.0880

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.000582

Gnomad4 SAS

AF:

0.0514

Gnomad4 FIN

AF:

0.213

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.111

Alfa

AF:

0.0571

Hom.:

Bravo

AF:

0.0739

Asia WGS

AF:

0.0210

AC:

AN:

3462

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over