rs7836586

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.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

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0130

Publications

13 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 8-60743131-G-A is Benign according to our data. Variant chr8-60743131-G-A is described in ClinVar as Benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
CHD7	NM_017780.4 link	c.1665+34G>A		intron_variant	Intron 2 of 37	ENST00000423902.7	NP_060250.2	Q9P2D1-1Q6ZWF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7 link	c.1665+34G>A		intron_variant	Intron 2 of 37	5	NM_017780.4	ENSP00000392028.1		Q9P2D1-1

Frequencies

GnomAD3 genomes

AF:

0.774

AC:

117740

AN:

152060

Hom.:

45855

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.809

AC:

181227

AN:

224094

AF XY:

0.812

show subpopulations

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 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.:

AF XY:

0.778

AC XY:

547502

AN XY:

703826

show subpopulations

African (AFR)

AF:

0.731

AC:

23635

AN:

32316

American (AMR)

AF:

0.815

AC:

34715

AN:

42584

Ashkenazi Jewish (ASJ)

AF:

0.764

AC:

19563

AN:

25612

East Asian (EAS)

AF:

0.948

AC:

36762

AN:

38760

South Asian (SAS)

AF:

0.910

AC:

75802

AN:

83326

European-Finnish (FIN)

AF:

0.833

AC:

42005

AN:

50446

Middle Eastern (MID)

AF:

0.738

AC:

4204

AN:

5700

European-Non Finnish (NFE)

AF:

0.754

AC:

811182

AN:

1075726

Other (OTH)

AF:

0.782

AC:

45981

AN:

58784

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

12679

25358

38037

50716

63395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19512

39024

58536

78048

97560

<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:

0.774

AC:

117808

AN:

152178

Hom.:

45876

Cov.:

AF XY:

0.782

AC XY:

58213

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.733

AC:

30404

AN:

41478

American (AMR)

AF:

0.795

AC:

12166

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.759

AC:

2634

AN:

3470

East Asian (EAS)

AF:

0.939

AC:

4866

AN:

5182

South Asian (SAS)

AF:

0.912

AC:

4408

AN:

4832

European-Finnish (FIN)

AF:

0.829

AC:

8782

AN:

10590

Middle Eastern (MID)

AF:

0.704

AC:

207

AN:

294

European-Non Finnish (NFE)

AF:

0.766

AC:

52064

AN:

68008

Other (OTH)

AF:

0.765

AC:

1617

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1379

2757

4136

5514

6893

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

866

1732

2598

3464

4330

<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:

0.764

Hom.:

9098

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

LINK: link

Submissions by phenotype

not provided

Benign:3

May 03, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

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

0.42

(source)

DANN

Benign

0.61

PhyloP100

-0.013

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

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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