rs4738824

Variant names:

• chr8-60777762-A-G
• rs4738824
• NM_017780.4:c.1666-3238A>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.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
• Publications: 9 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=-0.83).
• 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 rank	MANE	Protein	UniProt
CHD7	NM_017780.4	c.1666-3238A>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.1666-3238A>G		intron_variant	Intron 2 of 37	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

African (AFR) AF: 0.808 AC: 33531 AN: 41496

American (AMR) AF: 0.815 AC: 12457 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 2653 AN: 3472

East Asian (EAS) AF: 0.943 AC: 4889 AN: 5186

South Asian (SAS) AF: 0.917 AC: 4429 AN: 4828

European-Finnish (FIN) AF: 0.832 AC: 8797 AN: 10568

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.776 AC: 52779 AN: 68002

Other (OTH) AF: 0.781 AC: 1650 AN: 2112

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

Oct 15, 2013

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.56
PhyloP100		0.35
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: rs4738824; hg19: chr8-61690321;