rs7513548

Positions:

• chr1-6136457-G-A
• chr1-6136457-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.2696+60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,594,072 control chromosomes in the GnomAD database, including 156,087 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 0.43 (14579 hom., cov: 32)
  • Exomes 𝑓: 0.43 (141508 hom.)
• Consequence: CHD5 NM_015557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD5	NM_015557.3	c.2696+60C>T		intron_variant		ENST00000262450.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD5	ENST00000262450.8	c.2696+60C>T		intron_variant		1	NM_015557.3	P1
CHD5	ENST00000462991.5	c.843+60C>T		intron_variant, NMD_transcript_variant		1
CHD5	ENST00000496404.1	c.2696+60C>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64689 AN: 151932 Hom.: 14567 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.429

GnomAD4 exome AF: 0.433 AC: 624251 AN: 1442022 Hom.: 141508 AF XY: 0.437 AC XY: 313009 AN XY: 715564

Gnomad4 AFR exome AF: 0.338

Gnomad4 AMR exome AF: 0.486

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.829

Gnomad4 SAS exome AF: 0.597

Gnomad4 FIN exome AF: 0.535

Gnomad4 NFE exome AF: 0.399

Gnomad4 OTH exome AF: 0.447

GnomAD4 genome AF: 0.426 AC: 64748 AN: 152050 Hom.: 14579 Cov.: 32 AF XY: 0.435 AC XY: 32335 AN XY: 74314

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.431

Alfa AF: 0.419 Hom.: 1673

Bravo AF: 0.416

Asia WGS AF: 0.679 AC: 2357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.28
DANN	Benign	0.68

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: rs7513548; hg19: chr1-6196517; COSMIC: COSV52422478; COSMIC: COSV52422478;