rs1057510

Variant names:

• chr12-6574121-G-A
• rs1057510
• NM_001273.5:c.5362-852C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-6574121-G-A
• chr12-6574121-G-C
• chr12-6574121-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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]

CHD4 Gene-Disease associations (from GenCC):

• Sifrim-Hitz-Weiss syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ENSG00000285238 (HGNC:):

CHD4-AS1 (HGNC:58242):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CHD4	NM_001273.5	c.5362-852C>T		intron_variant	Intron 37 of 39	ENST00000544040.7	NP_001264.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD4	ENST00000544040.7	c.5362-852C>T		intron_variant	Intron 37 of 39	5	NM_001273.5	ENSP00000440542.2
ENSG00000285238	ENST00000644480.2	n.*443-852C>T		intron_variant	Intron 38 of 54			ENSP00000493629.2
ENSG00000285238	ENST00000646322.1	n.10-7504C>T		intron_variant	Intron 1 of 13			ENSP00000494949.1

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

African (AFR) AF: 0.604 AC: 25029 AN: 41428

American (AMR) AF: 0.185 AC: 2829 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 590 AN: 3470

East Asian (EAS) AF: 0.276 AC: 1426 AN: 5168

South Asian (SAS) AF: 0.226 AC: 1091 AN: 4822

European-Finnish (FIN) AF: 0.248 AC: 2616 AN: 10536

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11620 AN: 67982

Other (OTH) AF: 0.238 AC: 503 AN: 2114

Alfa AF: 0.210 Hom.: 14109

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
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1057510; hg19: chr12-6683287;