8-60678764-CGCGGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG

Variant names:

• chr8-60678764-C-CGCGGCGGCG
• rs886063023
• NM_017780.4:c.-475_-467dupGGCGGCGGC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1647 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1649 AN: 137566 Hom.: 20 Cov.: 0

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: 0 AN: 614 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 352

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0120 AC: 1647 AN: 137560 Hom.: 20 Cov.: 0 AF XY: 0.0117 AC XY: 781 AN XY: 66686

Gnomad4 AFR AF: 0.0205

Gnomad4 AMR AF: 0.0111

Gnomad4 ASJ AF: 0.00302

Gnomad4 EAS AF: 0.0129

Gnomad4 SAS AF: 0.0133

Gnomad4 FIN AF: 0.00570

Gnomad4 NFE AF: 0.00812

Gnomad4 OTH AF: 0.0143

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs886063023; hg19: chr8-61591323;