dbSNP rs17029184: CHD5:p.Ala1112Ala (chr1-6130255-C-T) – 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.3336G>A(p.Ala1112Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.084 in 1,613,710 control chromosomes in the GnomAD database, including 8,038 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 0.069 ( 639 hom., cov: 32)

Exomes 𝑓: 0.085 ( 7399 hom. )

Consequence

CHD5
NM_015557.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.67

Publications

13 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
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=-0.85).

BP7

Synonymous conserved (PhyloP=-4.67 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015557.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD5	NM_015557.3	MANE Select	c.3336G>A	p.Ala1112Ala	synonymous	Exon 22 of 42	NP_056372.1	Q8TDI0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHD5	ENST00000262450.8	TSL:1 MANE Select	c.3336G>A	p.Ala1112Ala	synonymous	Exon 22 of 42	ENSP00000262450.3	Q8TDI0
CHD5	ENST00000462991.5	TSL:1	n.1482G>A		non_coding_transcript_exon	Exon 11 of 31	ENSP00000466706.1	K7EMY3
CHD5	ENST00000496404.1	TSL:2	n.3336G>A		non_coding_transcript_exon	Exon 22 of 34	ENSP00000433676.1	F2Z2R5

Frequencies

GnomAD3 genomes

AF:

0.0695

AC:

10567

AN:

152004

Hom.:

643

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0159

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.0485

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.346

Gnomad SAS

AF:

0.0749

Gnomad FIN

AF:

0.0926

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0839

Gnomad OTH

AF:

0.0560

GnomAD2 exomes

AF:

0.0866

AC:

21742

AN:

251162

AF XY:

0.0867

show subpopulations

Gnomad AFR exome

AF:

0.0157

Gnomad AMR exome

AF:

0.0365

Gnomad ASJ exome

AF:

0.0389

Gnomad EAS exome

AF:

0.337

Gnomad FIN exome

AF:

0.0901

Gnomad NFE exome

AF:

0.0805

Gnomad OTH exome

AF:

0.0717

GnomAD4 exome

AF:

0.0855

AC:

124958

AN:

1461588

Hom.:

7399

Cov.:

AF XY:

0.0851

AC XY:

61867

AN XY:

727110

show subpopulations

African (AFR)

AF:

0.0120

AC:

401

AN:

33480

American (AMR)

AF:

0.0370

AC:

1655

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0375

AC:

981

AN:

26128

East Asian (EAS)

AF:

0.369

AC:

14634

AN:

39692

South Asian (SAS)

AF:

0.0700

AC:

6036

AN:

86244

European-Finnish (FIN)

AF:

0.0909

AC:

4852

AN:

53404

Middle Eastern (MID)

AF:

0.0179

AC:

103

AN:

5766

European-Non Finnish (NFE)

AF:

0.0822

AC:

91423

AN:

1111778

Other (OTH)

AF:

0.0807

AC:

4873

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

5667

11333

17000

22666

28333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3424

6848

10272

13696

17120

<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:

0.0694

AC:

10559

AN:

152122

Hom.:

639

Cov.:

AF XY:

0.0713

AC XY:

5301

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0159

AC:

659

AN:

41514

American (AMR)

AF:

0.0484

AC:

740

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0343

AC:

119

AN:

3470

East Asian (EAS)

AF:

0.346

AC:

1778

AN:

5144

South Asian (SAS)

AF:

0.0752

AC:

362

AN:

4814

European-Finnish (FIN)

AF:

0.0926

AC:

981

AN:

10590

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0838

AC:

5700

AN:

67982

Other (OTH)

AF:

0.0555

AC:

117

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

476

952

1427

1903

2379

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<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:

0.0690

Hom.:

458

Bravo

AF:

0.0639

Asia WGS

AF:

0.180

AC:

624

AN:

3478

EpiCase

AF:

0.0735

EpiControl

AF:

0.0732

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.7

(source)

DANN

Benign

0.74

PhyloP100

-4.7

Mutation Taster

=298/2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over