rs1017861

Variant names:

• chr8-60706154-A-G
• rs1017861
• NM_017780.4:c.-175+27072A>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.-175+27072A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,930 control chromosomes in the GnomAD database, including 25,057 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 0.52 (25057 hom., cov: 31)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4	c.-175+27072A>G		intron_variant	Intron 1 of 37	ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.-175+27072A>G		intron_variant	Intron 1 of 37	5	NM_017780.4	ENSP00000392028.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78987 AN: 151812 Hom.: 25049 Cov.: 31

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.520 AC: 79010 AN: 151930 Hom.: 25057 Cov.: 31 AF XY: 0.529 AC XY: 39249 AN XY: 74228

African (AFR) AF: 0.133 AC: 5495 AN: 41430

American (AMR) AF: 0.621 AC: 9472 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2146 AN: 3468

East Asian (EAS) AF: 0.740 AC: 3819 AN: 5158

South Asian (SAS) AF: 0.724 AC: 3484 AN: 4814

European-Finnish (FIN) AF: 0.686 AC: 7236 AN: 10546

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.669 AC: 45466 AN: 67938

Other (OTH) AF: 0.532 AC: 1123 AN: 2110

Alfa AF: 0.593 Hom.: 10278

Bravo AF: 0.496

Asia WGS AF: 0.670 AC: 2326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.077
DANN	Benign	0.39
PhyloP100		-2.1
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: rs1017861; hg19: chr8-61618713;