Variant chr8-60856636-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017780.4(CHD7):c.7356A>G(p.Thr2452=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0546 in 1,614,006 control chromosomes in the GnomAD database, including 2,654 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 156 hom., cov: 33)

Exomes 𝑓: 0.056 ( 2498 hom. )

Consequence

CHD7
NM_017780.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.53

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 8-60856636-A-G is Benign according to our data. Variant chr8-60856636-A-G is described in ClinVar as [Benign]. Clinvar id is 95811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-60856636-A-G is described in Lovd as [Benign]. Variant chr8-60856636-A-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD7	NM_017780.4 linkuse as main transcript	c.7356A>G	p.Thr2452=	synonymous_variant	34/38	ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7 linkuse as main transcript	c.7356A>G	p.Thr2452=	synonymous_variant	34/38	5	NM_017780.4	ENSP00000392028	P1	Q9P2D1-1

Frequencies

GnomAD3 genomes

AF:

0.0413

AC:

6282

AN:

152200

Hom.:

156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0141

Gnomad AMI

AF:

0.0780

Gnomad AMR

AF:

0.0289

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.0526

Gnomad SAS

AF:

0.0418

Gnomad FIN

AF:

0.0571

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0574

Gnomad OTH

AF:

0.0497

GnomAD3 exomes

AF:

0.0462

AC:

11522

AN:

249274

Hom.:

360

AF XY:

0.0475

AC XY:

6417

AN XY:

135236

show subpopulations

Gnomad AFR exome

AF:

0.0137

Gnomad AMR exome

AF:

0.0221

Gnomad ASJ exome

AF:

0.0258

Gnomad EAS exome

AF:

0.0516

Gnomad SAS exome

AF:

0.0433

Gnomad FIN exome

AF:

0.0591

Gnomad NFE exome

AF:

0.0572

Gnomad OTH exome

AF:

0.0484

GnomAD4 exome

AF:

0.0560

AC:

81855

AN:

1461688

Hom.:

2498

Cov.:

AF XY:

0.0556

AC XY:

40420

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.0128

Gnomad4 AMR exome

AF:

0.0234

Gnomad4 ASJ exome

AF:

0.0270

Gnomad4 EAS exome

AF:

0.0481

Gnomad4 SAS exome

AF:

0.0385

Gnomad4 FIN exome

AF:

0.0562

Gnomad4 NFE exome

AF:

0.0613

Gnomad4 OTH exome

AF:

0.0519

GnomAD4 genome

AF:

0.0412

AC:

6281

AN:

152318

Hom.:

156

Cov.:

AF XY:

0.0409

AC XY:

3043

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0141

Gnomad4 AMR

AF:

0.0288

Gnomad4 ASJ

AF:

0.0248

Gnomad4 EAS

AF:

0.0527

Gnomad4 SAS

AF:

0.0412

Gnomad4 FIN

AF:

0.0571

Gnomad4 NFE

AF:

0.0574

Gnomad4 OTH

AF:

0.0492

Alfa

AF:

0.0513

Hom.:

363

Bravo

AF:

0.0389

Asia WGS

AF:

0.0620

AC:

215

AN:

3478

EpiCase

AF:

0.0547

EpiControl

AF:

0.0562

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 22, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 23, 2017	p.Thr2452Thr in exon 34 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 5.65% (3768/66736) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs2272727). -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 27, 2017	- -

not provided

Benign:4

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	Sep 27, 2019	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

CHARGE syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2016

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

-0.49

CADD

Benign

8.4

DANN

Benign

0.73

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