rs161740

chr5-98869326-C-Achr5-98869326-C-T

Variant summary

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

The NM_001270.4(CHD1):c.4107+428G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 944,604 control chromosomes in the GnomAD database, including 36,839 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 0.27 (5908 hom., cov: 32)
  • Exomes 𝑓: 0.28 (30931 hom.)
• Consequence: CHD1 NM_001270.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD1	NM_001270.4	c.4107+428G>T		intron_variant		ENST00000614616.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD1	ENST00000614616.5	c.4107+428G>T		intron_variant		5	NM_001270.4	P2

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40705 AN: 151806 Hom.: 5904 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.0521

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.277 AC: 219273 AN: 792680 Hom.: 30931 Cov.: 12 AF XY: 0.276 AC XY: 101487 AN XY: 367680

Gnomad4 AFR exome AF: 0.371

Gnomad4 AMR exome AF: 0.184

Gnomad4 ASJ exome AF: 0.352

Gnomad4 EAS exome AF: 0.0466

Gnomad4 SAS exome AF: 0.182

Gnomad4 FIN exome AF: 0.166

Gnomad4 NFE exome AF: 0.277

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.268 AC: 40727 AN: 151924 Hom.: 5908 Cov.: 32 AF XY: 0.259 AC XY: 19219 AN XY: 74276

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.0521

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.268

Alfa AF: 0.262 Hom.: 6899

Bravo AF: 0.279

Asia WGS AF: 0.131 AC: 454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.71
Dann	Benign	0.58

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: rs161740; hg19: chr5-98205030;