1-147242777-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004284.6(CHD1L):c.74G>C(p.Arg25Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 1,269,940 control chromosomes in the GnomAD database, including 5,842 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 722 hom., cov: 33)

Exomes 𝑓: 0.091 ( 5120 hom. )

Consequence

CHD1L
NM_004284.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.773

Publications

19 publications found

Variant links:

Genes affected

CHD1L (HGNC:1916): (chromodomain helicase DNA binding protein 1 like) This gene encodes a DNA helicase protein involved in DNA repair. The protein converts ATP to add poly(ADP-ribose) as it regulates chromatin relaxation following DNA damage. Overexpression of this gene has been linked to several types of cancers. [provided by RefSeq, Feb 2017]

CHD1L links:

FMO5 (HGNC:3773): (flavin containing dimethylaniline monoxygenase 5) Metabolic N-oxidation of the diet-derived amino-trimethylamine (TMA) is mediated by flavin-containing monooxygenase and is subject to an inherited FMO3 polymorphism in man resulting in a small subpopulation with reduced TMA N-oxidation capacity resulting in fish odor syndrome Trimethylaminuria. Three forms of the enzyme, FMO1 found in fetal liver, FMO2 found in adult liver, and FMO3 are encoded by genes clustered in the 1q23-q25 region. Flavin-containing monooxygenases are NADPH-dependent flavoenzymes that catalyzes the oxidation of soft nucleophilic heteroatom centers in drugs, pesticides, and xenobiotics. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

FMO5 Gene-Disease associations (from GenCC):

congenital heart disease
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

FMO5 links:

ENSG00000237188 (HGNC:):

ENSG00000237188 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0018559396).

BP6

Variant 1-147242777-G-C is Benign according to our data. Variant chr1-147242777-G-C is described in ClinVar as [Benign]. Clinvar id is 1260082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD1L	NM_004284.6 link	c.74G>C	p.Arg25Pro	missense_variant	Exon 1 of 23	ENST00000369258.8	NP_004275.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD1L	ENST00000369258.8 link	c.74G>C	p.Arg25Pro	missense_variant	Exon 1 of 23	1	NM_004284.6	ENSP00000358262.4		Q86WJ1-1

Frequencies

GnomAD3 genomes

AF:

0.0922

AC:

14027

AN:

152100

Hom.:

717

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0736

Gnomad AMI

AF:

0.0571

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.0582

Gnomad EAS

AF:

0.158

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.0892

Gnomad NFE

AF:

0.0883

Gnomad OTH

AF:

0.0880

GnomAD2 exomes

AF:

0.120

AC:

5269

AN:

43920

AF XY:

0.120

show subpopulations

Gnomad AFR exome

AF:

0.0740

Gnomad AMR exome

AF:

0.159

Gnomad ASJ exome

AF:

0.0853

Gnomad EAS exome

AF:

0.197

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.104

Gnomad OTH exome

AF:

0.112

GnomAD4 exome

AF:

0.0912

AC:

101986

AN:

1117732

Hom.:

5120

Cov.:

AF XY:

0.0915

AC XY:

48522

AN XY:

530552

show subpopulations

African (AFR)

AF:

0.0736

AC:

1774

AN:

24110

American (AMR)

AF:

0.128

AC:

1408

AN:

10964

Ashkenazi Jewish (ASJ)

AF:

0.0692

AC:

1007

AN:

14562

East Asian (EAS)

AF:

0.213

AC:

6023

AN:

28340

South Asian (SAS)

AF:

0.140

AC:

2977

AN:

21330

European-Finnish (FIN)

AF:

0.126

AC:

4619

AN:

36790

Middle Eastern (MID)

AF:

0.0617

AC:

271

AN:

4394

European-Non Finnish (NFE)

AF:

0.0855

AC:

79690

AN:

932552

Other (OTH)

AF:

0.0944

AC:

4217

AN:

44690

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

5320

10640

15960

21280

26600

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0922

AC:

14039

AN:

152208

Hom.:

722

Cov.:

AF XY:

0.0948

AC XY:

7053

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0735

AC:

3056

AN:

41554

American (AMR)

AF:

0.110

AC:

1682

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0582

AC:

202

AN:

3470

East Asian (EAS)

AF:

0.158

AC:

816

AN:

5160

South Asian (SAS)

AF:

0.145

AC:

699

AN:

4828

European-Finnish (FIN)

AF:

0.124

AC:

1319

AN:

10606

Middle Eastern (MID)

AF:

0.0856

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0883

AC:

6000

AN:

67974

Other (OTH)

AF:

0.0889

AC:

188

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

668

1336

2005

2673

3341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0414

Hom.:

Bravo

AF:

0.0896

TwinsUK

AF:

0.0839

AC:

311

ALSPAC

AF:

0.0820

AC:

316

ESP6500AA

AF:

0.0675

AC:

284

ESP6500EA

AF:

0.0780

AC:

652

ExAC

AF:

0.0821

AC:

8833

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

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.016

T;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.51

T;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.0

L;L

PhyloP100

0.77

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.71

N;N

REVEL

Benign

0.29

Sift

Benign

0.094

T;T

Sift4G

Benign

0.083

T;T

Polyphen

0.0

B;B

Vest4

0.055

MPC

0.12

ClinPred

0.033

GERP RS

3.1

PromoterAI

0.016

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Varity_R

0.21

gMVP

0.53

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-147242777-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over