Genetic Variant NM_017780.4:c.-475_-467dupGGCGGCGGC (chr8-60678764-C-CGCGGCGGCG) – 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.-475_-467dupGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.012 ( 20 hom., cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CHD7
NM_017780.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.400

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:

Genome browser will be placed here

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 afr. GnomAd4 allele frequency = 0.012 (1647/137560) while in subpopulation AFR AF = 0.0205 (775/37724). AF 95% confidence interval is 0.0193. There are 20 homozygotes in GnomAd4. There are 781 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 20 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4 link	c.-475_-467dupGGCGGCGGC		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.-475_-467dupGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 38	5	NM_017780.4	ENSP00000392028.1		Q9P2D1-1

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1649

AN:

137566

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.00302

Gnomad EAS

AF:

0.0126

Gnomad SAS

AF:

0.0134

Gnomad FIN

AF:

0.00570

Gnomad MID

AF:

0.0317

Gnomad NFE

AF:

0.00812

Gnomad OTH

AF:

0.0149

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

614

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

352

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:

0.00

AC:

AN:

402

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

194

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.0120

AC:

1647

AN:

137560

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

781

AN XY:

66686

show subpopulations

African (AFR)

AF:

0.0205

AC:

775

AN:

37724

American (AMR)

AF:

0.0111

AC:

158

AN:

14238

Ashkenazi Jewish (ASJ)

AF:

0.00302

AC:

AN:

3308

East Asian (EAS)

AF:

0.0129

AC:

AN:

4434

South Asian (SAS)

AF:

0.0133

AC:

AN:

4438

European-Finnish (FIN)

AF:

0.00570

AC:

AN:

7366

Middle Eastern (MID)

AF:

0.0269

AC:

AN:

260

European-Non Finnish (NFE)

AF:

0.00812

AC:

512

AN:

63048

Other (OTH)

AF:

0.0143

AC:

AN:

1894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

152

229

305

381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00206

Hom.:

1058

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.40

Splicing

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

Publications

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NM_017780.4:c.-475_-467dupGGCGGCGGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over