rs4540437

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

19 publications found

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 Gene-Disease associations (from GenCC):

CHARGE syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Broad Center for Mendelian Genomics, ClinGen, G2P
hypogonadotropic hypogonadism 5 with or without anosmia
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
hypogonadotropic hypogonadism
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Kallmann syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Omenn syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CHD7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
CHD7	NM_017780.4 link	c.2238+39G>A		intron_variant	Intron 4 of 37	ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7 link	c.2238+39G>A		intron_variant	Intron 4 of 37	5	NM_017780.4	ENSP00000392028.1

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

GnomAD2 exomes

AF:

0.829

AC:

199676

AN:

240904

AF XY:

0.828

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 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

African (AFR)

AF:

0.936

AC:

30654

AN:

32750

American (AMR)

AF:

0.834

AC:

35725

AN:

42820

Ashkenazi Jewish (ASJ)

AF:

0.772

AC:

19773

AN:

25622

East Asian (EAS)

AF:

0.949

AC:

37545

AN:

39572

South Asian (SAS)

AF:

0.915

AC:

76616

AN:

83774

European-Finnish (FIN)

AF:

0.837

AC:

44245

AN:

52882

Middle Eastern (MID)

AF:

0.789

AC:

4499

AN:

5702

European-Non Finnish (NFE)

AF:

0.764

AC:

843119

AN:

1103886

Other (OTH)

AF:

0.804

AC:

48090

AN:

59778

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

10188

20377

30565

40754

50942

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20392

40784

61176

81568

101960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.838

AC:

127522

AN:

152150

Hom.:

53860

Cov.:

AF XY:

0.845

AC XY:

62823

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.932

AC:

38711

AN:

41522

American (AMR)

AF:

0.829

AC:

12681

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.764

AC:

2652

AN:

3472

East Asian (EAS)

AF:

0.943

AC:

4887

AN:

5184

South Asian (SAS)

AF:

0.918

AC:

4430

AN:

4826

European-Finnish (FIN)

AF:

0.832

AC:

8781

AN:

10556

Middle Eastern (MID)

AF:

0.776

AC:

228

AN:

294

European-Non Finnish (NFE)

AF:

0.776

AC:

52770

AN:

67984

Other (OTH)

AF:

0.816

AC:

1720

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1036

2072

3108

4144

5180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

886

1772

2658

3544

4430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.792

Hom.:

27573

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

Apr 20, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

CHARGE syndrome

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypogonadotropic hypogonadism 5 with or without anosmia

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.28

(source)

DANN

Benign

0.44

PhyloP100

-0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over