8-60678764-CGCGGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG

Variant names:

• chr8-60678764-C-CGCGGCGGCGGCGGCGGCGGCGGCG
• rs886063023
• NM_017780.4:c.-490_-467dupGGCGGCGGCGGCGGCGGCGGCGGC

Variant summary

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

The NM_017780.4(CHD7):​c.-490_-467dupGGCGGCGGCGGCGGCGGCGGCGGC 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 0.0010 (0 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 amr. gnomad4 allele frequency = 0.001 (138/137580) while in subpopulation AMR AF= 0.00176 (25/14242). AF 95% confidence interval is 0.00122. There are 0 homozygotes in gnomad4. There are 49 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 138 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4	c.-490_-467dupGGCGGCGGCGGCGGCGGCGGCGGC		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.-490_-467dupGGCGGCGGCGGCGGCGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 38	5	NM_017780.4	ENSP00000392028.1

Frequencies

GnomAD3 genomes AF: 0.00100 AC: 138 AN: 137586 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00176

Gnomad ASJ AF: 0.000605

Gnomad EAS AF: 0.000898

Gnomad SAS AF: 0.000672

Gnomad FIN AF: 0.000136

Gnomad MID AF: 0.00352

Gnomad NFE AF: 0.000745

Gnomad OTH AF: 0.000531

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR 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: 0.00100 AC: 138 AN: 137580 Hom.: 0 Cov.: 0 AF XY: 0.000735 AC XY: 49 AN XY: 66698

Gnomad4 AFR AF: 0.00143

Gnomad4 AMR AF: 0.00176

Gnomad4 ASJ AF: 0.000605

Gnomad4 EAS AF: 0.000902

Gnomad4 SAS AF: 0.000676

Gnomad4 FIN AF: 0.000136

Gnomad4 NFE AF: 0.000745

Gnomad4 OTH AF: 0.000528

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;