chr8-60778801-C-A

Variant names:

• chr8-60778801-C-A
• rs7017676
• NM_017780.4:c.1666-2199C>A

Variant summary

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

The NM_017780.4(CHD7):​c.1666-2199C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,192 control chromosomes in the GnomAD database, including 46,523 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 (46523 hom., cov: 33)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017780.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD7	NM_017780.4	MANE Select	c.1666-2199C>A		intron	N/A	NP_060250.2
	CHD7	NM_001316690.1		c.1666-2199C>A		intron	N/A	NP_001303619.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD7	ENST00000423902.7	TSL:5 MANE Select	c.1666-2199C>A		intron	N/A	ENSP00000392028.1
	CHD7	ENST00000524602.5	TSL:1	c.1666-2199C>A		intron	N/A	ENSP00000437061.1
	CHD7	ENST00000525508.1	TSL:5	c.1666-2199C>A		intron	N/A	ENSP00000436027.1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118676 AN: 152074 Hom.: 46500 Cov.: 33

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.875

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.780 AC: 118748 AN: 152192 Hom.: 46523 Cov.: 33 AF XY: 0.788 AC XY: 58646 AN XY: 74414

African (AFR) AF: 0.742 AC: 30805 AN: 41506

American (AMR) AF: 0.806 AC: 12327 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2590 AN: 3466

East Asian (EAS) AF: 0.943 AC: 4891 AN: 5188

South Asian (SAS) AF: 0.875 AC: 4218 AN: 4820

European-Finnish (FIN) AF: 0.833 AC: 8829 AN: 10598

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52599 AN: 68006

Other (OTH) AF: 0.761 AC: 1605 AN: 2110

Alfa AF: 0.776 Hom.: 5723

Bravo AF: 0.772

Asia WGS AF: 0.900 AC: 3130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.61
PhyloP100		-0.76
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: rs7017676; hg19: chr8-61691360;