rs2068096

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_017780.4(CHD7):c.6276G>A(p.Glu2092Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 1,613,912 control chromosomes in the GnomAD database, including 5,201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 2167 hom., cov: 32)

Exomes 𝑓: 0.047 ( 3034 hom. )

Consequence

CHD7
NM_017780.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 1.44

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 8-60853001-G-A is Benign according to our data. Variant chr8-60853001-G-A is described in ClinVar as [Benign]. Clinvar id is 95802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-60853001-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4 link	c.6276G>A	p.Glu2092Glu	synonymous_variant	Exon 31 of 38	ENST00000423902.7	NP_060250.2	Q9P2D1-1Q6ZWF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHD7	ENST00000423902.7 link	c.6276G>A	p.Glu2092Glu	synonymous_variant	Exon 31 of 38	5	NM_017780.4	ENSP00000392028.1	Q9P2D1-1
CHD7	ENST00000524602.5 link	c.1717-9228G>A		intron_variant	Intron 2 of 4	1		ENSP00000437061.1	Q9P2D1-4
CHD7	ENST00000695853.1 link	n.6276G>A		non_coding_transcript_exon_variant	Exon 31 of 37			ENSP00000512218.1	A0A8Q3WKT9

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17995

AN:

152084

Hom.:

2170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.306

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0637

Gnomad ASJ

AF:

0.0688

Gnomad EAS

AF:

0.0160

Gnomad SAS

AF:

0.0478

Gnomad FIN

AF:

0.0756

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0406

Gnomad OTH

AF:

0.103

GnomAD3 exomes

AF:

0.0611

AC:

15230

AN:

249160

Hom.:

1081

AF XY:

0.0572

AC XY:

7733

AN XY:

135166

show subpopulations

Gnomad AFR exome

AF:

0.317

Gnomad AMR exome

AF:

0.0359

Gnomad ASJ exome

AF:

0.0749

Gnomad EAS exome

AF:

0.0132

Gnomad SAS exome

AF:

0.0464

Gnomad FIN exome

AF:

0.0804

Gnomad NFE exome

AF:

0.0407

Gnomad OTH exome

AF:

0.0565

GnomAD4 exome

AF:

0.0466

AC:

68184

AN:

1461710

Hom.:

3034

Cov.:

AF XY:

0.0458

AC XY:

33281

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.315

Gnomad4 AMR exome

AF:

0.0399

Gnomad4 ASJ exome

AF:

0.0754

Gnomad4 EAS exome

AF:

0.0165

Gnomad4 SAS exome

AF:

0.0474

Gnomad4 FIN exome

AF:

0.0784

Gnomad4 NFE exome

AF:

0.0368

Gnomad4 OTH exome

AF:

0.0592

GnomAD4 genome

AF:

0.118

AC:

18002

AN:

152202

Hom.:

2167

Cov.:

AF XY:

0.117

AC XY:

8712

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.305

Gnomad4 AMR

AF:

0.0636

Gnomad4 ASJ

AF:

0.0688

Gnomad4 EAS

AF:

0.0159

Gnomad4 SAS

AF:

0.0472

Gnomad4 FIN

AF:

0.0756

Gnomad4 NFE

AF:

0.0406

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.0606

Hom.:

869

Bravo

AF:

0.123

Asia WGS

AF:

0.0440

AC:

154

AN:

3478

EpiCase

AF:

0.0376

EpiControl

AF:

0.0381

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 03, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 24, 2018

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 23, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Glu2092Glu in exon 31 of CHD7: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 30.76% (3016/9804) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs2068096). -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 25, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CHARGE syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Mar 16, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Hypogonadotropic hypogonadism 5 with or without anosmia

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

2.1

DANN

Benign

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over