Variant rs4540437 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.2238+39G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 1,598,936 control chromosomes in the GnomAD database, including 505,823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 53860 hom., cov: 30)

Exomes 𝑓: 0.79 ( 451963 hom. )

Consequence

CHD7
NM_017780.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.215

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=-0.89).

BP6

Variant 8-60795166-G-A is Benign according to our data. Variant chr8-60795166-G-A is described in ClinVar as [Benign]. Clinvar id is 158325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 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.2238+39G>A		intron_variant		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.2238+39G>A		intron_variant		5	NM_017780.4	ENSP00000392028	P1	Q9P2D1-1

Frequencies

GnomAD3 genomes

AF:

0.838

AC:

127419

AN:

152032

Hom.:

53814

Cov.:

show subpopulations

Gnomad AFR

AF:

0.932

Gnomad AMI

AF:

0.731

Gnomad AMR

AF:

0.829

Gnomad ASJ

AF:

0.764

Gnomad EAS

AF:

0.943

Gnomad SAS

AF:

0.918

Gnomad FIN

AF:

0.832

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.776

Gnomad OTH

AF:

0.814

GnomAD3 exomes

AF:

0.829

AC:

199676

AN:

240904

Hom.:

83341

AF XY:

0.828

AC XY:

108253

AN XY:

130696

show subpopulations

Gnomad AFR exome

AF:

0.939

Gnomad AMR exome

AF:

0.837

Gnomad ASJ exome

AF:

0.771

Gnomad EAS exome

AF:

0.941

Gnomad SAS exome

AF:

0.916

Gnomad FIN exome

AF:

0.841

Gnomad NFE exome

AF:

0.775

Gnomad OTH exome

AF:

0.794

GnomAD4 exome

AF:

0.788

AC:

1140266

AN:

1446786

Hom.:

451963

Cov.:

AF XY:

0.791

AC XY:

568845

AN XY:

719134

show subpopulations

Gnomad4 AFR exome

AF:

0.936

Gnomad4 AMR exome

AF:

0.834

Gnomad4 ASJ exome

AF:

0.772

Gnomad4 EAS exome

AF:

0.949

Gnomad4 SAS exome

AF:

0.915

Gnomad4 FIN exome

AF:

0.837

Gnomad4 NFE exome

AF:

0.764

Gnomad4 OTH exome

AF:

0.804

GnomAD4 genome

AF:

0.838

AC:

127522

AN:

152150

Hom.:

53860

Cov.:

AF XY:

0.845

AC XY:

62823

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.932

Gnomad4 AMR

AF:

0.829

Gnomad4 ASJ

AF:

0.764

Gnomad4 EAS

AF:

0.943

Gnomad4 SAS

AF:

0.918

Gnomad4 FIN

AF:

0.832

Gnomad4 NFE

AF:

0.776

Gnomad4 OTH

AF:

0.816

Alfa

AF:

0.793

Hom.:

24973

Bravo

AF:

0.836

Asia WGS

AF:

0.930

AC:

3232

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Apr 20, 2020	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -

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

0.28

DANN

Benign

0.44

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