17-7884893-CGAGGAGGAG-CGAGGAG

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS1

The NM_001437504.1(CHD3):c.104_106delAGG(p.Glu35del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00619 in 1,232,916 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0069 ( 0 hom. )

Consequence

CHD3
NM_001437504.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.28

Publications

2 publications found

Variant links:

Genes affected

CHD3 (HGNC:1918): (chromodomain helicase DNA binding protein 3) This gene encodes a member of the CHD family of proteins which are characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. This protein is one of the components of a histone deacetylase complex referred to as the Mi-2/NuRD complex which participates in the remodeling of chromatin by deacetylating histones. Chromatin remodeling is essential for many processes including transcription. Autoantibodies against this protein are found in a subset of patients with dermatomyositis. Three alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

CHD3 links:

NAA38 (HGNC:28212): (N-alpha-acetyltransferase 38, NatC auxiliary subunit) Involved in negative regulation of apoptotic process. Located in cytoplasm and nucleoplasm. Part of NatC complex. Colocalizes with polysome. [provided by Alliance of Genome Resources, Apr 2022]

NAA38 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001437504.1

BP6

Variant 17-7884893-CGAG-C is Benign according to our data. Variant chr17-7884893-CGAG-C is described in ClinVar as Benign. ClinVar VariationId is 2647418.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000322 (45/139660) while in subpopulation AFR AF = 0.000845 (32/37852). AF 95% confidence interval is 0.000615. There are 0 homozygotes in GnomAd4. There are 22 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001437504.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHD3	NM_001437504.1	c.104_106delAGG	p.Glu35del	disruptive_inframe_deletion	Exon 1 of 40	NP_001424433.1	A0A8V8TR54
CHD3	NM_001005271.3	c.104_106delAGG	p.Glu35del	disruptive_inframe_deletion	Exon 1 of 40	NP_001005271.2	Q12873-3
CHD3	NM_001437509.1	c.104_106delAGG	p.Glu35del	disruptive_inframe_deletion	Exon 1 of 40	NP_001424438.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHD3	ENST00000700753.1		c.104_106delAGG	p.Glu35del	disruptive_inframe_deletion	Exon 1 of 40	ENSP00000515165.1	A0A8V8TR54
CHD3	ENST00000380358.9	TSL:2	c.104_106delAGG	p.Glu35del	disruptive_inframe_deletion	Exon 1 of 40	ENSP00000369716.4	Q12873-3
NAA38	ENST00000576861.5	TSL:3	c.-167+269_-167+271delCTC		intron	N/A	ENSP00000461545.1	I3L4V0

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

139660

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000698

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000226

Gnomad FIN

AF:

0.000674

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000633

Gnomad OTH

AF:

0.000525

GnomAD2 exomes

AF:

0.0131

AC:

774

AN:

59150

AF XY:

0.0134

show subpopulations

Gnomad AFR exome

AF:

0.00830

Gnomad AMR exome

AF:

0.0143

Gnomad ASJ exome

AF:

0.0120

Gnomad EAS exome

AF:

0.0113

Gnomad FIN exome

AF:

0.0160

Gnomad NFE exome

AF:

0.0123

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.00694

AC:

7590

AN:

1093256

Hom.:

AF XY:

0.00752

AC XY:

4050

AN XY:

538318

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00684

AC:

152

AN:

22224

American (AMR)

AF:

0.0130

AC:

279

AN:

21462

Ashkenazi Jewish (ASJ)

AF:

0.00959

AC:

159

AN:

16584

East Asian (EAS)

AF:

0.00747

AC:

168

AN:

22496

South Asian (SAS)

AF:

0.0158

AC:

851

AN:

53872

European-Finnish (FIN)

AF:

0.0117

AC:

364

AN:

31072

Middle Eastern (MID)

AF:

0.00580

AC:

AN:

3102

European-Non Finnish (NFE)

AF:

0.00600

AC:

5282

AN:

880010

Other (OTH)

AF:

0.00747

AC:

317

AN:

42434

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.252

Heterozygous variant carriers

1076

2152

3227

4303

5379

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

154

308

462

616

770

<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:

0.000322

AC:

AN:

139660

Hom.:

Cov.:

AF XY:

0.000324

AC XY:

AN XY:

67922

show subpopulations

African (AFR)

AF:

0.000845

AC:

AN:

37852

American (AMR)

AF:

0.0000698

AC:

AN:

14320

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3278

East Asian (EAS)

AF:

0.00

AC:

AN:

4660

South Asian (SAS)

AF:

0.000226

AC:

AN:

4420

European-Finnish (FIN)

AF:

0.000674

AC:

AN:

8902

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.0000633

AC:

AN:

63220

Other (OTH)

AF:

0.000525

AC:

AN:

1906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00762

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.3

Mutation Taster

=78/22

polymorphism

(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