rs5891777

chr8-60800567-A-ATGGACT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_017780.4(CHD7):c.2376+43_2376+48dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 1,550,796 control chromosomes in the GnomAD database, including 469,561 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (45749 hom., cov: 0)
  • Exomes 𝑓: 0.78 (423812 hom.)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.541

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 -16 ACMG points.

• BP6: Variant 8-60800567-A-ATGGACT is Benign according to our data. Variant chr8-60800567-A-ATGGACT is described in ClinVar as [Likely_benign]. Clinvar id is 260894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD7	NM_017780.4	c.2376+43_2376+48dup		intron_variant		ENST00000423902.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD7	ENST00000423902.7	c.2376+43_2376+48dup		intron_variant		5	NM_017780.4	P1

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117300 AN: 151208 Hom.: 45725 Cov.: 0

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.875

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.754

GnomAD3 exomes AF: 0.801 AC: 166321 AN: 207726 Hom.: 67011 AF XY: 0.802 AC XY: 89817 AN XY: 112028

Gnomad AFR exome AF: 0.732

Gnomad AMR exome AF: 0.820

Gnomad ASJ exome AF: 0.748

Gnomad EAS exome AF: 0.939

Gnomad SAS exome AF: 0.868

Gnomad FIN exome AF: 0.837

Gnomad NFE exome AF: 0.765

Gnomad OTH exome AF: 0.782

GnomAD4 exome AF: 0.776 AC: 1085308 AN: 1399472 Hom.: 423812 Cov.: 25 AF XY: 0.778 AC XY: 537772 AN XY: 691640

Gnomad4 AFR exome AF: 0.731

Gnomad4 AMR exome AF: 0.819

Gnomad4 ASJ exome AF: 0.755

Gnomad4 EAS exome AF: 0.949

Gnomad4 SAS exome AF: 0.864

Gnomad4 FIN exome AF: 0.835

Gnomad4 NFE exome AF: 0.760

Gnomad4 OTH exome AF: 0.783

GnomAD4 genome AF: 0.776 AC: 117374 AN: 151324 Hom.: 45749 Cov.: 0 AF XY: 0.784 AC XY: 57925 AN XY: 73918

Gnomad4 AFR AF: 0.729

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.746

Gnomad4 EAS AF: 0.943

Gnomad4 SAS AF: 0.875

Gnomad4 FIN AF: 0.831

Gnomad4 NFE AF: 0.772

Gnomad4 OTH AF: 0.756

Alfa AF: 0.762 Hom.: 9294

Asia WGS AF: 0.900 AC: 3129 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

CHARGE syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

- -

Hypogonadotropic hypogonadism 5 with or without anosmia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

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: rs5891777; hg19: chr8-61713126;