8-60777762-A-G

Position:

• chr8-60777762-A-G

Variant summary

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

The NM_017780.4(CHD7):​c.1666-3238A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 152,162 control chromosomes in the GnomAD database, including 49,130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: 𝑓 0.80 (49130 hom., cov: 32)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.354

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]

CHD7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD7	NM_017780.4	c.1666-3238A>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.1666-3238A>G		intron_variant		5	NM_017780.4	ENSP00000392028.1

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121992 AN: 152044 Hom.: 49099 Cov.: 32

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.779

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

GnomAD4 genome AF: 0.802 AC: 122076 AN: 152162 Hom.: 49130 Cov.: 32 AF XY: 0.810 AC XY: 60267 AN XY: 74376

Gnomad4 AFR AF: 0.808

Gnomad4 AMR AF: 0.815

Gnomad4 ASJ AF: 0.764

Gnomad4 EAS AF: 0.943

Gnomad4 SAS AF: 0.917

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.776

Gnomad4 OTH AF: 0.781

Alfa AF: 0.788 Hom.: 5902

Bravo AF: 0.796

Asia WGS AF: 0.924 AC: 3211 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Scoliosis, isolated, susceptibility to, 3 Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Oct 15, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.56

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: rs4738824; hg19: chr8-61690321;