rs1057510

chr12-6574121-G-Achr12-6574121-G-Cchr12-6574121-G-T

Variant summary

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

The NM_001273.5(CHD4):c.5362-852C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 151,986 control chromosomes in the GnomAD database, including 9,645 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 0.30 (9645 hom., cov: 32)
• Consequence: CHD4 NM_001273.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335

Genes affected

CHD4 (HGNC:1919): (chromodomain helicase DNA binding protein 4) The product of this gene belongs to the SNF2/RAD54 helicase family. It represents the main component of the nucleosome remodeling and deacetylase complex and plays an important role in epigenetic transcriptional repression. Patients with dermatomyositis develop antibodies against this protein. Somatic mutations in this gene are associated with serous endometrial tumors. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD4	NM_001273.5	c.5362-852C>T		intron_variant		ENST00000544040.7
CHD4	NM_001297553.2	c.5341-852C>T		intron_variant
CHD4	NM_001363606.2	c.5329-852C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD4	ENST00000544040.7	c.5362-852C>T		intron_variant		5	NM_001273.5	A1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45794 AN: 151868 Hom.: 9620 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.238

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.302 AC: 45868 AN: 151986 Hom.: 9645 Cov.: 32 AF XY: 0.302 AC XY: 22421 AN XY: 74282

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.238

Alfa AF: 0.185 Hom.: 5992

Bravo AF: 0.309

Asia WGS AF: 0.291 AC: 1012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	7.0
Dann	Benign	0.73

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: rs1057510; hg19: chr12-6683287;