Genetic Variant NM_017780.4:c.-472_-467delGGCGGC (chr8-60678764-CGCGGCG-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_017780.4(CHD7):c.-472_-467delGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00931 in 138,184 control chromosomes in the GnomAD database, including 12 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0091 ( 10 hom., cov: 0)

Exomes 𝑓: 0.047 ( 2 hom. )

Consequence

CHD7
NM_017780.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.88

Publications

2 publications found

Variant links:

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

CHD7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00914 (1257/137570) while in subpopulation SAS AF = 0.0352 (156/4434). AF 95% confidence interval is 0.0307. There are 10 homozygotes in GnomAd4. There are 615 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4 link	c.-472_-467delGGCGGC		5_prime_UTR_variant	Exon 1 of 38	ENST00000423902.7	NP_060250.2	Q9P2D1-1Q6ZWF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7 link	c.-472_-467delGGCGGC		5_prime_UTR_variant	Exon 1 of 38	5	NM_017780.4	ENSP00000392028.1		Q9P2D1-1

Frequencies

GnomAD3 genomes

AF:

0.00911

AC:

1254

AN:

137576

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00252

Gnomad AMI

AF:

0.0141

Gnomad AMR

AF:

0.0178

Gnomad ASJ

AF:

0.00544

Gnomad EAS

AF:

0.000674

Gnomad SAS

AF:

0.0348

Gnomad FIN

AF:

0.00353

Gnomad MID

AF:

0.0176

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.00798

GnomAD4 exome

AF:

0.0472

AC:

AN:

614

Hom.:

AF XY:

0.0313

AC XY:

AN XY:

352

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0522

AC:

AN:

402

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0361

AC:

AN:

194

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.581

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00914

AC:

1257

AN:

137570

Hom.:

Cov.:

AF XY:

0.00922

AC XY:

615

AN XY:

66694

show subpopulations

African (AFR)

AF:

0.00252

AC:

AN:

37734

American (AMR)

AF:

0.0179

AC:

255

AN:

14242

Ashkenazi Jewish (ASJ)

AF:

0.00544

AC:

AN:

3306

East Asian (EAS)

AF:

0.000677

AC:

AN:

4434

South Asian (SAS)

AF:

0.0352

AC:

156

AN:

4434

European-Finnish (FIN)

AF:

0.00353

AC:

AN:

7368

Middle Eastern (MID)

AF:

0.0192

AC:

AN:

260

European-Non Finnish (NFE)

AF:

0.0107

AC:

672

AN:

63050

Other (OTH)

AF:

0.00793

AC:

AN:

1892

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

112

169

225

281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00544

Hom.:

1058

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_017780.4:c.-472_-467delGGCGGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over