rs12758341

Positions:

• chr1-6101899-G-A
• chr1-6101899-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015557.3(CHD5):​c.*3575C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 319,548 control chromosomes in the GnomAD database, including 2,293 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 0.096 (1013 hom., cov: 32)
  • Exomes 𝑓: 0.11 (1280 hom.)
• Consequence: CHD5 NM_015557.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD5	NM_015557.3	c.*3575C>T		3_prime_UTR_variant	42/42	ENST00000262450.8	NP_056372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD5	ENST00000262450	c.*3575C>T		3_prime_UTR_variant	42/42	1	NM_015557.3	ENSP00000262450.3

Frequencies

GnomAD3 genomes AF: 0.0956 AC: 14553 AN: 152158 Hom.: 1019 Cov.: 32

Gnomad AFR AF: 0.0225

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0803

Gnomad ASJ AF: 0.0997

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0847

GnomAD3 exomes AF: 0.110 AC: 2972 AN: 27070 Hom.: 222 AF XY: 0.111 AC XY: 1764 AN XY: 15918

Gnomad AFR exome AF: 0.00855

Gnomad AMR exome AF: 0.0601

Gnomad ASJ exome AF: 0.0871

Gnomad EAS exome AF: 0.321

Gnomad SAS exome AF: 0.120

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.0881

GnomAD4 exome AF: 0.114 AC: 19124 AN: 167272 Hom.: 1280 Cov.: 0 AF XY: 0.116 AC XY: 11131 AN XY: 95590

Gnomad4 AFR exome AF: 0.0198

Gnomad4 AMR exome AF: 0.0638

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.355

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.0955 AC: 14544 AN: 152276 Hom.: 1013 Cov.: 32 AF XY: 0.0972 AC XY: 7239 AN XY: 74460

Gnomad4 AFR AF: 0.0224

Gnomad4 AMR AF: 0.0801

Gnomad4 ASJ AF: 0.0997

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.0838

Alfa AF: 0.0935 Hom.: 206

Bravo AF: 0.0889

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.59

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: rs12758341; hg19: chr1-6161959; COSMIC: COSV51238665; COSMIC: COSV51238665;