chr8-60678785-GGCGGCA-G

Position:

• chr8-60678785-GGCGGCA-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_017780.4(CHD7):​c.-466_-461delAGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 140,306 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0014 (0 hom.)
• Consequence: CHD7 NM_017780.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 0.786

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 138 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD7	NM_017780.4	c.-466_-461delAGCGGC		5_prime_UTR_variant	1/38	ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902	c.-466_-461delAGCGGC		5_prime_UTR_variant	1/38	5	NM_017780.4	ENSP00000392028.1

Frequencies

GnomAD3 genomes AF: 0.000999 AC: 138 AN: 138180 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00204

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00101

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000838

Gnomad SAS AF: 0.000683

Gnomad FIN AF: 0.000130

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000545

Gnomad OTH AF: 0.00158

GnomAD4 exome AF: 0.00141 AC: 3 AN: 2128 Hom.: 0 AF XY: 0.00270 AC XY: 3 AN XY: 1112

Gnomad4 AFR exome AF: 0.0238

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00124

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0179

GnomAD4 genome AF: 0.000999 AC: 138 AN: 138178 Hom.: 0 Cov.: 0 AF XY: 0.000894 AC XY: 60 AN XY: 67112

Gnomad4 AFR AF: 0.00203

Gnomad4 AMR AF: 0.00101

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000841

Gnomad4 SAS AF: 0.000688

Gnomad4 FIN AF: 0.000130

Gnomad4 NFE AF: 0.000545

Gnomad4 OTH AF: 0.00157

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

CHARGE syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Hypogonadism with anosmia Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs886063025; hg19: chr8-61591344;