Genetic Variant NM_015557.3:c.2379C>T (chr1-6142185-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_015557.3(CHD5):c.2379C>T(p.Asn793Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,613,830 control chromosomes in the GnomAD database, including 13,082 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 0.10 ( 1045 hom., cov: 32)

Exomes 𝑓: 0.12 ( 12037 hom. )

Consequence

CHD5
NM_015557.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.280

Publications

14 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP7

Synonymous conserved (PhyloP=-0.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD5	NM_015557.3 link	c.2379C>T	p.Asn793Asn	synonymous_variant	Exon 15 of 42	ENST00000262450.8	NP_056372.1	Q8TDI0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHD5	ENST00000262450.8 link	c.2379C>T	p.Asn793Asn	synonymous_variant	Exon 15 of 42	1	NM_015557.3	ENSP00000262450.3	Q8TDI0
CHD5	ENST00000462991.5 link	n.525C>T		non_coding_transcript_exon_variant	Exon 4 of 31	1		ENSP00000466706.1	K7EMY3
CHD5	ENST00000496404.1 link	n.2379C>T		non_coding_transcript_exon_variant	Exon 15 of 34	2		ENSP00000433676.1	F2Z2R5

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15508

AN:

152042

Hom.:

1046

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0482

Gnomad AMI

AF:

0.141

Gnomad AMR

AF:

0.0669

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.345

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.0860

GnomAD2 exomes

AF:

0.119

AC:

29931

AN:

251468

AF XY:

0.121

show subpopulations

Gnomad AFR exome

AF:

0.0493

Gnomad AMR exome

AF:

0.0487

Gnomad ASJ exome

AF:

0.105

Gnomad EAS exome

AF:

0.344

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.119

AC:

174159

AN:

1461668

Hom.:

12037

Cov.:

AF XY:

0.120

AC XY:

86959

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.0456

AC:

1526

AN:

33480

American (AMR)

AF:

0.0497

AC:

2222

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

2682

AN:

26136

East Asian (EAS)

AF:

0.367

AC:

14576

AN:

39698

South Asian (SAS)

AF:

0.136

AC:

11718

AN:

86250

European-Finnish (FIN)

AF:

0.116

AC:

6171

AN:

53408

Middle Eastern (MID)

AF:

0.0621

AC:

358

AN:

5768

European-Non Finnish (NFE)

AF:

0.115

AC:

127935

AN:

1111824

Other (OTH)

AF:

0.115

AC:

6971

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

8064

16128

24193

32257

40321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4776

9552

14328

19104

23880

<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:

0.102

AC:

15523

AN:

152162

Hom.:

1045

Cov.:

AF XY:

0.104

AC XY:

7708

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0486

AC:

2020

AN:

41532

American (AMR)

AF:

0.0667

AC:

1020

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

363

AN:

3466

East Asian (EAS)

AF:

0.345

AC:

1777

AN:

5156

South Asian (SAS)

AF:

0.147

AC:

709

AN:

4816

European-Finnish (FIN)

AF:

0.122

AC:

1297

AN:

10592

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.118

AC:

8017

AN:

67992

Other (OTH)

AF:

0.0851

AC:

180

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

701

1401

2102

2802

3503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

368

552

736

920

<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:

0.105

Hom.:

1760

Bravo

AF:

0.0951

Asia WGS

AF:

0.212

AC:

735

AN:

3478

EpiCase

AF:

0.109

EpiControl

AF:

0.106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

1.5

(source)

DANN

Benign

0.79

PhyloP100

-0.28

Mutation Taster

=299/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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