rs1483207

Positions:

• chr8-60754721-C-G

Variant summary

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

The NM_017780.4(CHD7):​c.1665+11624C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,236 control chromosomes in the GnomAD database, including 2,051 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 0.14 (2051 hom., cov: 32)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.751

Genes affected

CHD7 (HGNC:20626): (chromodomain helicase DNA binding protein 7) This gene encodes a protein that contains several helicase family domains. Mutations in this gene have been found in some patients with the CHARGE syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD7	NM_017780.4	c.1665+11624C>G		intron_variant		ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.1665+11624C>G		intron_variant		5	NM_017780.4	ENSP00000392028	P1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22018 AN: 152118 Hom.: 2049 Cov.: 32

Gnomad AFR AF: 0.0348

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.145 AC: 22025 AN: 152236 Hom.: 2051 Cov.: 32 AF XY: 0.145 AC XY: 10794 AN XY: 74444

Gnomad4 AFR AF: 0.0347

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.136

Alfa AF: 0.165 Hom.: 307

Bravo AF: 0.136

Asia WGS AF: 0.249 AC: 862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	12
DANN	Benign	0.60

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: rs1483207; hg19: chr8-61667280;