dbSNP rs17489787: CHD5:c.1803-7G>C (chr1-6144162-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_015557.3(CHD5):c.1803-7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,614,006 control chromosomes in the GnomAD database, including 12,495 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1606 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10889 hom. )

Consequence

CHD5
NM_015557.3 splice_region, intron

Scores

Splicing: ADA: 0.0006094

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.646

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD5	NM_015557.3 link	c.1803-7G>C		splice_region_variant, intron_variant	Intron 11 of 41	ENST00000262450.8	NP_056372.1	Q8TDI0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHD5	ENST00000262450.8 link	c.1803-7G>C	splice_region_variant, intron_variant	Intron 11 of 41	1	NM_015557.3	ENSP00000262450.3	Q8TDI0
CHD5	ENST00000496404.1 link	n.1803-7G>C	splice_region_variant, intron_variant	Intron 11 of 33	2		ENSP00000433676.1	F2Z2R5
CHD5	ENST00000462991.5 link	n.-59G>C	upstream_gene_variant		1		ENSP00000466706.1	K7EMY3

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20827

AN:

152086

Hom.:

1590

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.0967

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.128

GnomAD3 exomes

AF:

0.136

AC:

34137

AN:

251376

Hom.:

2756

AF XY:

0.134

AC XY:

18249

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.202

Gnomad AMR exome

AF:

0.188

Gnomad ASJ exome

AF:

0.108

Gnomad EAS exome

AF:

0.131

Gnomad SAS exome

AF:

0.218

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.0997

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.115

AC:

167911

AN:

1461802

Hom.:

10889

Cov.:

AF XY:

0.116

AC XY:

84495

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.204

Gnomad4 AMR exome

AF:

0.177

Gnomad4 ASJ exome

AF:

0.105

Gnomad4 EAS exome

AF:

0.113

Gnomad4 SAS exome

AF:

0.219

Gnomad4 FIN exome

AF:

0.101

Gnomad4 NFE exome

AF:

0.103

Gnomad4 OTH exome

AF:

0.117

GnomAD4 genome

AF:

0.137

AC:

20864

AN:

152204

Hom.:

1606

Cov.:

AF XY:

0.138

AC XY:

10239

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.203

Gnomad4 AMR

AF:

0.128

Gnomad4 ASJ

AF:

0.106

Gnomad4 EAS

AF:

0.135

Gnomad4 SAS

AF:

0.230

Gnomad4 FIN

AF:

0.0967

Gnomad4 NFE

AF:

0.101

Gnomad4 OTH

AF:

0.132

Alfa

AF:

0.108

Hom.:

360

Bravo

AF:

0.140

Asia WGS

AF:

0.195

AC:

677

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

7.7

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00061

dbscSNV1_RF

Benign

0.012

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over