rs17489787

chr1-6144162-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_015557.3(CHD5):c.1803-7G>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,614,006 control chromosomes in the GnomAD database, including 12,495 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1606 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10889 hom.)
• Consequence: CHD5 NM_015557.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0006094
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.646

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD5	NM_015557.3	c.1803-7G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000262450.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD5	ENST00000262450.8	c.1803-7G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_015557.3	P1
CHD5	ENST00000496404.1	c.1803-7G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20827 AN: 152086 Hom.: 1590 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.0967

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.128

GnomAD3 exomes AF: 0.136 AC: 34137 AN: 251376 Hom.: 2756 AF XY: 0.134 AC XY: 18249 AN XY: 135862

Gnomad AFR exome AF: 0.202

Gnomad AMR exome AF: 0.188

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.131

Gnomad SAS exome AF: 0.218

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.0997

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.115 AC: 167911 AN: 1461802 Hom.: 10889 Cov.: 47 AF XY: 0.116 AC XY: 84495 AN XY: 727204

Gnomad4 AFR exome AF: 0.204

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.137 AC: 20864 AN: 152204 Hom.: 1606 Cov.: 32 AF XY: 0.138 AC XY: 10239 AN XY: 74416

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.0967

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.132

Alfa AF: 0.108 Hom.: 360

Bravo AF: 0.140

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
Cadd	Benign	7.7
Dann	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00061
dbscSNV1_RF	Benign	0.012
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: rs17489787; hg19: chr1-6204222; COSMIC: COSV52415239; COSMIC: COSV52415239;