rs2273032

Variant names:

• chr1-6142185-G-A
• rs2273032
• NM_015557.3:c.2379C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-6142185-G-A
• chr1-6142185-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• Publications: 14 publications found

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)

ACMG classification

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	c.2379C>T	p.Asn793Asn	synonymous_variant	Exon 15 of 42	ENST00000262450.8	NP_056372.1

Ensembl

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

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

GnomAD2 exomes AF: 0.119 AC: 29931 AN: 251468 AF XY: 0.121

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

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

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

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: 11 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8017 AN: 67992

Other (OTH) AF: 0.0851 AC: 180 AN: 2114

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
DANN	Benign	0.79
PhyloP100		-0.28
Mutation Taster		=299/1	polymorphism (auto)

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