8-60770633-A-T

Variant names:

• chr8-60770633-A-T
• rs7002806
• NM_017780.4:c.1666-10367A>T

Variant summary

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

The NM_017780.4(CHD7):​c.1666-10367A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,174 control chromosomes in the GnomAD database, including 46,373 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 (46373 hom., cov: 32)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 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.1666-10367A>T		intron	N/A	NP_060250.2
	CHD7	NM_001316690.1		c.1666-10367A>T		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.1666-10367A>T		intron	N/A	ENSP00000392028.1
	CHD7	ENST00000524602.5	TSL:1	c.1666-10367A>T		intron	N/A	ENSP00000437061.1
	CHD7	ENST00000525508.1	TSL:5	c.1666-10367A>T		intron	N/A	ENSP00000436027.1

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118382 AN: 152056 Hom.: 46350 Cov.: 32

Gnomad AFR AF: 0.725

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: 0.768

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

GnomAD4 genome AF: 0.778 AC: 118451 AN: 152174 Hom.: 46373 Cov.: 32 AF XY: 0.787 AC XY: 58542 AN XY: 74414

African (AFR) AF: 0.724 AC: 30059 AN: 41494

American (AMR) AF: 0.806 AC: 12319 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 2669 AN: 3472

East Asian (EAS) AF: 0.940 AC: 4883 AN: 5194

South Asian (SAS) AF: 0.918 AC: 4421 AN: 4816

European-Finnish (FIN) AF: 0.832 AC: 8810 AN: 10590

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

European-Non Finnish (NFE) AF: 0.776 AC: 52774 AN: 68000

Other (OTH) AF: 0.770 AC: 1627 AN: 2112

Alfa AF: 0.773 Hom.: 5689

Bravo AF: 0.768

Asia WGS AF: 0.912 AC: 3169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	9.4
DANN	Benign	0.39
PhyloP100		-0.099
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: rs7002806; hg19: chr8-61683192;