rs2092507

Positions:

• chr1-6104348-G-A
• chr1-6104348-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.*1126C>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 0.13 in 152,288 control chromosomes in the GnomAD database, including 1,367 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 0.13 (1366 hom., cov: 32)
  • Exomes 𝑓: 0.13 (1 hom.)
• Consequence: CHD5 NM_015557.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.991

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD5	NM_015557.3	c.*1126C>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.*1126C>T		3_prime_UTR_variant	42/42	1	NM_015557.3	ENSP00000262450.3

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19784 AN: 152004 Hom.: 1366 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.127 AC: 21 AN: 166 Hom.: 1 Cov.: 0 AF XY: 0.0965 AC XY: 11 AN XY: 114

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.130 AC: 19788 AN: 152122 Hom.: 1366 Cov.: 32 AF XY: 0.130 AC XY: 9692 AN XY: 74346

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.0847

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.126

Alfa AF: 0.135 Hom.: 485

Bravo AF: 0.130

Asia WGS AF: 0.197 AC: 685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.43
DANN	Benign	0.43

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: rs2092507; hg19: chr1-6164408;