Variant 5-98856564-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_001270.4(CHD1):c.4949C>T(p.Thr1650Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,613,760 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 14 hom. )

Consequence

CHD1
NM_001270.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.52

Variant links:

Genes affected

CHD1 (HGNC:1915): (chromodomain helicase DNA binding protein 1) The CHD family of proteins is characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. CHD genes alter gene expression possibly by modification of chromatin structure thus altering access of the transcriptional apparatus to its chromosomal DNA template. [provided by RefSeq, Jul 2008]

CHD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CHD1. . Trascript score misZ 3.2778 (greater than threshold 3.09). GenCC has associacion of gene with Pilarowski-Bjornsson syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055195987).

BP6

Variant 5-98856564-G-A is Benign according to our data. Variant chr5-98856564-G-A is described in ClinVar as [Benign]. Clinvar id is 2655604.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 194 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD1	NM_001270.4 linkuse as main transcript	c.4949C>T	p.Thr1650Met	missense_variant	36/36	ENST00000614616.5	NP_001261.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD1	ENST00000614616.5 linkuse as main transcript	c.4949C>T	p.Thr1650Met	missense_variant	36/36	5	NM_001270.4	ENSP00000483667	P2	O14646-1

Frequencies

GnomAD3 genomes

AF:

0.00126

AC:

191

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00726

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00177

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00187

AC:

469

AN:

251158

Hom.:

AF XY:

0.00225

AC XY:

306

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000956

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00673

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00184

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00168

AC:

2454

AN:

1461596

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

1324

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00604

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.00156

Gnomad4 OTH exome

AF:

0.00177

GnomAD4 genome

AF:

0.00127

AC:

194

AN:

152164

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

106

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00726

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.00177

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00161

Hom.:

Bravo

AF:

0.00100

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00195

AC:

237

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00240

EpiControl

AF:

0.00243

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CHD1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

CHD1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.058

T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.085

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.68

.;T

MetaRNN

Benign

0.0055

T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.89

.;N

REVEL

Benign

0.22

Sift

Benign

0.035

.;D

Sift4G

Benign

0.097

T;T

Polyphen

0.82

P;P

Vest4

0.066

MVP

0.62

MPC

0.059

ClinPred

0.013

GERP RS

4.7

Varity_R

0.027

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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