chr8-60761996-T-C

Variant names:

• chr8-60761996-T-C
• rs2875984
• NM_017780.4:c.1665+18899T>C

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+18899T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 151,932 control chromosomes in the GnomAD database, including 46,581 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 0.78 (46581 hom., cov: 29)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75
• Publications: 6 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4	c.1665+18899T>C		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+18899T>C		intron_variant	Intron 2 of 37	5	NM_017780.4	ENSP00000392028.1

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118594 AN: 151814 Hom.: 46561 Cov.: 29

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.770

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

GnomAD4 genome AF: 0.781 AC: 118663 AN: 151932 Hom.: 46581 Cov.: 29 AF XY: 0.789 AC XY: 58606 AN XY: 74266

African (AFR) AF: 0.734 AC: 30368 AN: 41400

American (AMR) AF: 0.806 AC: 12314 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 2666 AN: 3466

East Asian (EAS) AF: 0.941 AC: 4855 AN: 5162

South Asian (SAS) AF: 0.918 AC: 4419 AN: 4814

European-Finnish (FIN) AF: 0.832 AC: 8785 AN: 10560

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.776 AC: 52741 AN: 67942

Other (OTH) AF: 0.772 AC: 1628 AN: 2110

Alfa AF: 0.776 Hom.: 7736

Bravo AF: 0.771

Asia WGS AF: 0.912 AC: 3169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.13
DANN	Benign	0.42
PhyloP100		-2.8
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: rs2875984; hg19: chr8-61674555;