chr8-60678764-C-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG

Variant names:

• chr8-60678764-C-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG
• rs886063023
• NM_017780.4:c.-467_-466insGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_017780.4(CHD7):​c.-467_-466insGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00044 (0 hom., cov: 0)
• Consequence: CHD7 NM_017780.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000436 (60/137576) while in subpopulation AMR AF = 0.00211 (30/14242). AF 95% confidence interval is 0.00152. There are 0 homozygotes in GnomAd4. There are 44 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4	c.-467_-466insGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 38	ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.-467_-466insGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 38	5	NM_017780.4	ENSP00000392028.1

Frequencies

GnomAD3 genomes AF: 0.000436 AC: 60 AN: 137582 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000398

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00211

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000448

Gnomad FIN AF: 0.000136

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000190

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.000436 AC: 60 AN: 137576 Hom.: 0 Cov.: 0 AF XY: 0.000660 AC XY: 44 AN XY: 66698

African (AFR) AF: 0.000398 AC: 15 AN: 37734

American (AMR) AF: 0.00211 AC: 30 AN: 14242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3308

East Asian (EAS) AF: 0.00 AC: 0 AN: 4432

South Asian (SAS) AF: 0.000451 AC: 2 AN: 4438

European-Finnish (FIN) AF: 0.000136 AC: 1 AN: 7368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.000190 AC: 12 AN: 63050

Other (OTH) AF: 0.00 AC: 0 AN: 1894

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

Other links and lift over

dbSNP: rs886063023; hg19: chr8-61591323;