dbSNP rs2092507: CHD5:c.*1126C>T (chr1-6104348-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015557.3(CHD5):c.*1126C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,288 control chromosomes in the GnomAD database, including 1,367 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1366 hom., cov: 32)

Exomes 𝑓: 0.13 ( 1 hom. )

Consequence

CHD5
NM_015557.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.991

Publications

4 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD5	NM_015557.3 link	c.*1126C>T		3_prime_UTR_variant	Exon 42 of 42	ENST00000262450.8	NP_056372.1	Q8TDI0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD5	ENST00000262450.8 link	c.*1126C>T		3_prime_UTR_variant	Exon 42 of 42	1	NM_015557.3	ENSP00000262450.3		Q8TDI0

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19784

AN:

152004

Hom.:

1366

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.0847

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.125

GnomAD4 exome

AF:

0.127

AC:

AN:

166

Hom.:

Cov.:

AF XY:

0.0965

AC XY:

AN XY:

114

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.108

AC:

AN:

130

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.130

AC:

19788

AN:

152122

Hom.:

1366

Cov.:

AF XY:

0.130

AC XY:

9692

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.107

AC:

4437

AN:

41504

American (AMR)

AF:

0.150

AC:

2293

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0847

AC:

294

AN:

3470

East Asian (EAS)

AF:

0.193

AC:

994

AN:

5148

South Asian (SAS)

AF:

0.196

AC:

944

AN:

4826

European-Finnish (FIN)

AF:

0.161

AC:

1702

AN:

10596

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.129

AC:

8734

AN:

67966

Other (OTH)

AF:

0.126

AC:

266

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

900

1800

2701

3601

4501

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

232

464

696

928

1160

<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:

0.134

Hom.:

578

Bravo

AF:

0.130

Asia WGS

AF:

0.197

AC:

685

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.43

(source)

DANN

Benign

0.43

PhyloP100

-0.99

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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