rs7000766

Variant names:

• chr8-60745274-A-G
• rs7000766
• NM_017780.4:c.1665+2177A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017780.4(CHD7):​c.1665+2177A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 152,186 control chromosomes in the GnomAD database, including 51,294 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 0.82 (51294 hom., cov: 31)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• CHARGE syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Broad Center for Mendelian Genomics, ClinGen, G2P
• hypogonadotropic hypogonadism 5 with or without anosmia

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Omenn syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4	c.1665+2177A>G		intron_variant	Intron 2 of 37	ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.1665+2177A>G		intron_variant	Intron 2 of 37	5	NM_017780.4	ENSP00000392028.1

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124467 AN: 152066 Hom.: 51257 Cov.: 31

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.800

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

GnomAD4 genome AF: 0.818 AC: 124561 AN: 152186 Hom.: 51294 Cov.: 31 AF XY: 0.825 AC XY: 61370 AN XY: 74408

African (AFR) AF: 0.887 AC: 36834 AN: 41544

American (AMR) AF: 0.812 AC: 12412 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.759 AC: 2634 AN: 3470

East Asian (EAS) AF: 0.939 AC: 4844 AN: 5158

South Asian (SAS) AF: 0.915 AC: 4414 AN: 4824

European-Finnish (FIN) AF: 0.829 AC: 8777 AN: 10586

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52079 AN: 67996

Other (OTH) AF: 0.801 AC: 1694 AN: 2114

Alfa AF: 0.800 Hom.: 8524

Bravo AF: 0.814

Asia WGS AF: 0.917 AC: 3186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.82
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7000766; hg19: chr8-61657833;