Variant chr1-6144101-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_015557.3(CHD5):c.1857C>T(p.Tyr619=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,614,092 control chromosomes in the GnomAD database, including 10,743 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.096 ( 918 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9825 hom. )

Consequence

CHD5
NM_015557.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.39

Variant links:

Genes affected

CHD5 (HGNC:16816): (chromodomain helicase DNA binding protein 5) This gene encodes a member of the chromodomain helicase DNA-binding protein family. Members of this family are characterized by a chromodomain, a helicase ATP-binding domain and an additional functional domain. This gene encodes a neuron-specific protein that may function in chromatin remodeling and gene transcription. This gene is a potential tumor suppressor gene that may play a role in the development of neuroblastoma. [provided by RefSeq, Feb 2012]

CHD5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 1-6144101-G-A is Benign according to our data. Variant chr1-6144101-G-A is described in ClinVar as [Benign]. Clinvar id is 3059081.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD5	NM_015557.3 linkuse as main transcript	c.1857C>T	p.Tyr619=	synonymous_variant	12/42	ENST00000262450.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CHD5	ENST00000262450.8 linkuse as main transcript	c.1857C>T	p.Tyr619=	synonymous_variant	12/42	1	NM_015557.3	P1
CHD5	ENST00000462991.5 linkuse as main transcript	c.6C>T	p.Tyr2=	synonymous_variant, NMD_transcript_variant	1/31	1
CHD5	ENST00000496404.1 linkuse as main transcript	c.1857C>T	p.Tyr619=	synonymous_variant, NMD_transcript_variant	12/34	2

Frequencies

GnomAD3 genomes

AF:

0.0961

AC:

14618

AN:

152116

Hom.:

914

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0315

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.0231

Gnomad SAS

AF:

0.0961

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.210

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.127

GnomAD3 exomes

AF:

0.117

AC:

29383

AN:

251484

Hom.:

2071

AF XY:

0.118

AC XY:

16055

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0284

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.218

Gnomad EAS exome

AF:

0.0195

Gnomad SAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.122

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.111

AC:

162684

AN:

1461858

Hom.:

9825

Cov.:

AF XY:

0.112

AC XY:

81619

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0295

Gnomad4 AMR exome

AF:

0.165

Gnomad4 ASJ exome

AF:

0.214

Gnomad4 EAS exome

AF:

0.0163

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.114

Gnomad4 NFE exome

AF:

0.112

Gnomad4 OTH exome

AF:

0.115

GnomAD4 genome

AF:

0.0962

AC:

14638

AN:

152234

Hom.:

918

Cov.:

AF XY:

0.0973

AC XY:

7240

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0315

Gnomad4 AMR

AF:

0.165

Gnomad4 ASJ

AF:

0.209

Gnomad4 EAS

AF:

0.0228

Gnomad4 SAS

AF:

0.0972

Gnomad4 FIN

AF:

0.116

Gnomad4 NFE

AF:

0.115

Gnomad4 OTH

AF:

0.129

Alfa

AF:

0.122

Hom.:

2120

Bravo

AF:

0.0989

Asia WGS

AF:

0.0810

AC:

281

AN:

3478

EpiCase

AF:

0.129

EpiControl

AF:

0.131

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CHD5-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 26, 2023

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.3

DANN

Benign

0.60

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