rs161942

Positions:

• chr5-98868016-A-G

Variant summary

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

The NM_001270.4(CHD1):​c.4248+479T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,290 control chromosomes in the GnomAD database, including 10,004 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 0.33 (10004 hom., cov: 28)
• Consequence: CHD1 NM_001270.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.847

Genes affected

CHD1 (HGNC:1915): (chromodomain helicase DNA binding protein 1) The CHD family of proteins is characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. CHD genes alter gene expression possibly by modification of chromatin structure thus altering access of the transcriptional apparatus to its chromosomal DNA template. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD1	NM_001270.4	c.4248+479T>C		intron_variant		ENST00000614616.5	NP_001261.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD1	ENST00000614616.5	c.4248+479T>C		intron_variant		5	NM_001270.4	ENSP00000483667	P2

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50269 AN: 151174 Hom.: 9993 Cov.: 28

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.0523

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.333 AC: 50312 AN: 151290 Hom.: 10004 Cov.: 28 AF XY: 0.321 AC XY: 23730 AN XY: 73896

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.0522

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.316

Alfa AF: 0.301 Hom.: 981

Bravo AF: 0.351

Asia WGS AF: 0.156 AC: 541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.1
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs161942; hg19: chr5-98203720;