Variant chr5-98856391-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

The NM_001270.4(CHD1):c.5122C>T(p.Arg1708Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000192 in 1,606,840 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

CHD1
NM_001270.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 7.18

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 Likely_benign. Variant got -3 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.

BS2

High AC in GnomAd4 at 32 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD1	NM_001270.4 linkuse as main transcript	c.5122C>T	p.Arg1708Trp	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.5122C>T	p.Arg1708Trp	missense_variant	36/36	5	NM_001270.4	ENSP00000483667	P2	O14646-1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000918

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000184

AC:

AN:

250424

Hom.:

AF XY:

0.000214

AC XY:

AN XY:

135404

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.000318

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000190

AC:

277

AN:

1454816

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

145

AN XY:

722496

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000238

Gnomad4 OTH exome

AF:

0.0000666

GnomAD4 genome

AF:

0.000210

AC:

AN:

152024

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.000918

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.000196

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000189

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2021

The c.5122C>T (p.R1708W) alteration is located in exon 35 (coding exon 35) of the CHD1 gene. This alteration results from a C to T substitution at nucleotide position 5122, causing the arginine (R) at amino acid position 1708 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Clinical Genetics Laboratory, Skane University Hospital Lund

Sep 21, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.097

T;T

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

.;D

M_CAP

Benign

0.084

MetaRNN

Uncertain

0.55

D;D

MetaSVM

Uncertain

0.77

MutationAssessor

Uncertain

2.6

M;M

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-2.8

.;D

REVEL

Uncertain

0.63

Sift

Uncertain

0.026

.;D

Sift4G

Benign

0.073

T;T

Polyphen

1.0

D;D

Vest4

0.67

MVP

0.78

MPC

0.13

ClinPred

0.37

GERP RS

4.6

Varity_R

0.17

gMVP

0.67

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

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