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

Variant summary

Our verdict is Benign. The variant received -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

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

parenti-mignot neurodevelopmental syndrome
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
schizophrenia
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

CHD5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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

GnomAD2 exomes

AF:

0.136

AC:

34137

AN:

251376

AF XY:

0.134

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 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

African (AFR)

AF:

0.204

AC:

6845

AN:

33480

American (AMR)

AF:

0.177

AC:

7931

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

2756

AN:

26128

East Asian (EAS)

AF:

0.113

AC:

4489

AN:

39700

South Asian (SAS)

AF:

0.219

AC:

18861

AN:

86252

European-Finnish (FIN)

AF:

0.101

AC:

5367

AN:

53384

Middle Eastern (MID)

AF:

0.0576

AC:

332

AN:

5768

European-Non Finnish (NFE)

AF:

0.103

AC:

114255

AN:

1111978

Other (OTH)

AF:

0.117

AC:

7075

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

8053

16105

24158

32210

40263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4492

8984

13476

17968

22460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.137

AC:

20864

AN:

152204

Hom.:

1606

Cov.:

AF XY:

0.138

AC XY:

10239

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.203

AC:

8435

AN:

41514

American (AMR)

AF:

0.128

AC:

1951

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

367

AN:

3470

East Asian (EAS)

AF:

0.135

AC:

700

AN:

5178

South Asian (SAS)

AF:

0.230

AC:

1109

AN:

4822

European-Finnish (FIN)

AF:

0.0967

AC:

1024

AN:

10592

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.101

AC:

6846

AN:

68012

Other (OTH)

AF:

0.132

AC:

279

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

945

1890

2834

3779

4724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.90

PhyloP100

0.65

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over