8-60702325-G-T

Variant names:

• chr8-60702325-G-T
• rs9643371
• NM_017780.4:c.-175+23243G>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.-175+23243G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 152,066 control chromosomes in the GnomAD database, including 35,260 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 0.66 (35260 hom., cov: 32)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.623
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.912 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.-175+23243G>T		intron	N/A	NP_060250.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD7	ENST00000423902.7	TSL:5 MANE Select	c.-175+23243G>T		intron	N/A	ENSP00000392028.1
	CHD7	ENST00000700671.1		c.-175+22087G>T		intron	N/A	ENSP00000515139.1
	CHD7	ENST00000526846.1	TSL:2	c.-175+22534G>T		intron	N/A	ENSP00000436492.1

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100327 AN: 151948 Hom.: 35253 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.660 AC: 100364 AN: 152066 Hom.: 35260 Cov.: 32 AF XY: 0.670 AC XY: 49828 AN XY: 74332

African (AFR) AF: 0.406 AC: 16812 AN: 41404

American (AMR) AF: 0.739 AC: 11303 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2508 AN: 3470

East Asian (EAS) AF: 0.934 AC: 4844 AN: 5184

South Asian (SAS) AF: 0.841 AC: 4060 AN: 4830

European-Finnish (FIN) AF: 0.808 AC: 8546 AN: 10580

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 50043 AN: 67982

Other (OTH) AF: 0.663 AC: 1396 AN: 2106

Alfa AF: 0.680 Hom.: 4775

Bravo AF: 0.639

Asia WGS AF: 0.844 AC: 2932 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.60
DANN	Benign	0.48
PhyloP100		-0.62
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: rs9643371; hg19: chr8-61614884;