rs7843033

Positions:

• chr8-60759956-A-C
• chr8-60759956-A-G
• chr8-60759956-A-T

Variant summary

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

The NM_017780.4(CHD7):​c.1665+16859A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 151,994 control chromosomes in the GnomAD database, including 45,491 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 0.77 (45491 hom., cov: 30)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.652

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD7	NM_017780.4	c.1665+16859A>C		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+16859A>C		intron_variant		5	NM_017780.4	ENSP00000392028	P1

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117152 AN: 151876 Hom.: 45471 Cov.: 30

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.941

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.760

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

GnomAD4 genome AF: 0.771 AC: 117219 AN: 151994 Hom.: 45491 Cov.: 30 AF XY: 0.779 AC XY: 57906 AN XY: 74292

Gnomad4 AFR AF: 0.723

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.760

Gnomad4 EAS AF: 0.941

Gnomad4 SAS AF: 0.914

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.765

Gnomad4 OTH AF: 0.762

Alfa AF: 0.763 Hom.: 6501

Bravo AF: 0.761

Asia WGS AF: 0.909 AC: 3160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.81
DANN	Benign	0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7843033; hg19: chr8-61672515;