rs772711535

Variant names:

• chr17-7884848-G-A
• rs772711535
• NM_001437504.1:c.42G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001437504.1(CHD3):​c.42G>A​(p.Glu14Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000757 in 1,115,704 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 25)
  • Exomes 𝑓: 0.00081 (4 hom.)
• Consequence: CHD3 NM_001437504.1 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.665
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 17-7884848-G-A is Benign according to our data. Variant chr17-7884848-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 932351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.665 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000383 (57/148738) while in subpopulation SAS AF = 0.00492 (23/4674). AF 95% confidence interval is 0.00336. There are 0 homozygotes in GnomAd4. There are 38 alleles in the male GnomAd4 subpopulation. Median coverage is 25. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 4 AD,AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD3	NM_001437504.1		c.42G>A	p.Glu14Glu	synonymous	Exon 1 of 40	NP_001424433.1	A0A8V8TR54
	CHD3	NM_001005271.3		c.42G>A	p.Glu14Glu	synonymous	Exon 1 of 40	NP_001005271.2	Q12873-3
	CHD3	NM_001437509.1		c.42G>A	p.Glu14Glu	synonymous	Exon 1 of 40	NP_001424438.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD3	ENST00000700753.1		c.42G>A	p.Glu14Glu	synonymous	Exon 1 of 40	ENSP00000515165.1	A0A8V8TR54
	CHD3	ENST00000380358.9	TSL:2	c.42G>A	p.Glu14Glu	synonymous	Exon 1 of 40	ENSP00000369716.4	Q12873-3
	NAA38	ENST00000576861.5	TSL:3	c.-167+317C>T		intron	N/A	ENSP00000461545.1	I3L4V0

Frequencies

GnomAD3 genomes AF: 0.000390 AC: 58 AN: 148634 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000332

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00513

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000407

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00197 AC: 157 AN: 79592 AF XY: 0.00253

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000617

Gnomad ASJ exome AF: 0.000162

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000725

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000815 AC: 788 AN: 966966 Hom.: 4 Cov.: 13 AF XY: 0.000989 AC XY: 483 AN XY: 488584

African (AFR) AF: 0.00 AC: 0 AN: 20910

American (AMR) AF: 0.000148 AC: 4 AN: 27076

Ashkenazi Jewish (ASJ) AF: 0.0000511 AC: 1 AN: 19586

East Asian (EAS) AF: 0.0000377 AC: 1 AN: 26500

South Asian (SAS) AF: 0.00672 AC: 398 AN: 59234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30612

Middle Eastern (MID) AF: 0.00566 AC: 17 AN: 3006

European-Non Finnish (NFE) AF: 0.000447 AC: 330 AN: 738706

Other (OTH) AF: 0.000895 AC: 37 AN: 41336

GnomAD4 genome AF: 0.000383 AC: 57 AN: 148738 Hom.: 0 Cov.: 25 AF XY: 0.000524 AC XY: 38 AN XY: 72482

African (AFR) AF: 0.0000491 AC: 2 AN: 40754

American (AMR) AF: 0.000331 AC: 5 AN: 15084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3390

East Asian (EAS) AF: 0.00 AC: 0 AN: 4984

South Asian (SAS) AF: 0.00492 AC: 23 AN: 4674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.000407 AC: 27 AN: 66308

Other (OTH) AF: 0.00 AC: 0 AN: 2064

Alfa AF: 0.000437 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.96
PhyloP100		0.67
PromoterAI		0.16	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs772711535; hg19: chr17-7788166;