rs2273032

Positions:

• chr1-6142185-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015557.3(CHD5):​c.2379C>T​(p.Asn793=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CHD5	NM_015557.3	c.2379C>T	p.Asn793=	synonymous_variant	15/42	ENST00000262450.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD5	ENST00000262450.8	c.2379C>T	p.Asn793=	synonymous_variant	15/42	1	NM_015557.3	P1
CHD5	ENST00000462991.5	c.528C>T	p.Asn176=	synonymous_variant, NMD_transcript_variant	4/31	1
CHD5	ENST00000496404.1	c.2379C>T	p.Asn793=	synonymous_variant, NMD_transcript_variant	15/34	2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15508 AN: 152042 Hom.: 1046 Cov.: 32

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

GnomAD3 exomes AF: 0.119 AC: 29931 AN: 251468 Hom.: 2449 AF XY: 0.121 AC XY: 16505 AN XY: 135902

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 SAS exome AF: 0.139

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.: 33 AF XY: 0.120 AC XY: 86959 AN XY: 727152

Gnomad4 AFR exome AF: 0.0456

Gnomad4 AMR exome AF: 0.0497

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.367

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.115

GnomAD4 genome AF: 0.102 AC: 15523 AN: 152162 Hom.: 1045 Cov.: 32 AF XY: 0.104 AC XY: 7708 AN XY: 74388

Gnomad4 AFR AF: 0.0486

Gnomad4 AMR AF: 0.0667

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.0851

Alfa AF: 0.107 Hom.: 1514

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
DANN	Benign	0.79

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

LitVar

Other links and lift over

dbSNP: rs2273032; hg19: chr1-6202245; COSMIC: COSV52414711;