rs7836586

Positions:

• chr8-60743131-G-A
• chr8-60743131-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017780.4(CHD7):​c.1665+34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 1,565,432 control chromosomes in the GnomAD database, including 471,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (45876 hom., cov: 33)
  • Exomes 𝑓: 0.77 (425539 hom.)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0130

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 8-60743131-G-A is Benign according to our data. Variant chr8-60743131-G-A is described in ClinVar as [Benign]. Clinvar id is 158324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD7	NM_017780.4	c.1665+34G>A		intron_variant		ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.1665+34G>A		intron_variant		5	NM_017780.4	ENSP00000392028.1

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117740 AN: 152060 Hom.: 45855 Cov.: 33

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.763

GnomAD3 exomes AF: 0.809 AC: 181227 AN: 224094 Hom.: 73652 AF XY: 0.812 AC XY: 98565 AN XY: 121314

Gnomad AFR exome AF: 0.743

Gnomad AMR exome AF: 0.819

Gnomad ASJ exome AF: 0.762

Gnomad EAS exome AF: 0.939

Gnomad SAS exome AF: 0.911

Gnomad FIN exome AF: 0.836

Gnomad NFE exome AF: 0.765

Gnomad OTH exome AF: 0.777

GnomAD4 exome AF: 0.774 AC: 1093849 AN: 1413254 Hom.: 425539 Cov.: 24 AF XY: 0.778 AC XY: 547502 AN XY: 703826

Gnomad4 AFR exome AF: 0.731

Gnomad4 AMR exome AF: 0.815

Gnomad4 ASJ exome AF: 0.764

Gnomad4 EAS exome AF: 0.948

Gnomad4 SAS exome AF: 0.910

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.754

Gnomad4 OTH exome AF: 0.782

GnomAD4 genome AF: 0.774 AC: 117808 AN: 152178 Hom.: 45876 Cov.: 33 AF XY: 0.782 AC XY: 58213 AN XY: 74416

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.759

Gnomad4 EAS AF: 0.939

Gnomad4 SAS AF: 0.912

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.765

Alfa AF: 0.765 Hom.: 8890

Bravo AF: 0.764

Asia WGS AF: 0.908 AC: 3155 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	May 03, 2020	- -

not specified Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
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

- -

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7836586; hg19: chr8-61655690;