NM_017780.4:c.4533+46A>G

Variant names:

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.4533+46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 1,534,680 control chromosomes in the GnomAD database, including 455,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 46707 hom., cov: 32)

Exomes 𝑓: 0.77 ( 408618 hom. )

Consequence

CHD7
NM_017780.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.52

Publications

15 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=-0.92).

BP6

Variant 8-60838301-A-G is Benign according to our data. Variant chr8-60838301-A-G is described in ClinVar as Benign. ClinVar VariationId is 158327.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.4533+46A>G		intron_variant	Intron 19 of 37	ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CHD7	ENST00000423902.7 link	c.4533+46A>G	intron_variant	Intron 19 of 37	5	NM_017780.4	ENSP00000392028.1
CHD7	ENST00000524602.5 link	c.1717-23928A>G	intron_variant	Intron 2 of 4	1		ENSP00000437061.1
CHD7	ENST00000695853.1 link	n.4533+46A>G	intron_variant	Intron 19 of 36			ENSP00000512218.1

Frequencies

GnomAD3 genomes

AF:

0.782

AC:

118854

AN:

152050

Hom.:

46676

Cov.:

show subpopulations

Gnomad AFR

AF:

0.780

Gnomad AMI

AF:

0.703

Gnomad AMR

AF:

0.792

Gnomad ASJ

AF:

0.743

Gnomad EAS

AF:

0.939

Gnomad SAS

AF:

0.898

Gnomad FIN

AF:

0.829

Gnomad MID

AF:

0.729

Gnomad NFE

AF:

0.757

Gnomad OTH

AF:

0.755

GnomAD2 exomes

AF:

0.804

AC:

148968

AN:

185184

AF XY:

0.807

show subpopulations

Gnomad AFR exome

AF:

0.789

Gnomad AMR exome

AF:

0.812

Gnomad ASJ exome

AF:

0.752

Gnomad EAS exome

AF:

0.939

Gnomad FIN exome

AF:

0.839

Gnomad NFE exome

AF:

0.755

Gnomad OTH exome

AF:

0.768

GnomAD4 exome

AF:

0.767

AC:

1060240

AN:

1382512

Hom.:

408618

Cov.:

AF XY:

0.770

AC XY:

527835

AN XY:

685512

show subpopulations

African (AFR)

AF:

0.784

AC:

24939

AN:

31808

American (AMR)

AF:

0.808

AC:

29973

AN:

37110

Ashkenazi Jewish (ASJ)

AF:

0.755

AC:

18954

AN:

25106

East Asian (EAS)

AF:

0.938

AC:

35376

AN:

37716

South Asian (SAS)

AF:

0.889

AC:

70404

AN:

79170

European-Finnish (FIN)

AF:

0.833

AC:

42389

AN:

50858

Middle Eastern (MID)

AF:

0.759

AC:

4274

AN:

5632

European-Non Finnish (NFE)

AF:

0.746

AC:

788895

AN:

1057336

Other (OTH)

AF:

0.779

AC:

45036

AN:

57776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

11602

23205

34807

46410

58012

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19286

38572

57858

77144

96430

<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:

0.782

AC:

118938

AN:

152168

Hom.:

46707

Cov.:

AF XY:

0.790

AC XY:

58806

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.780

AC:

32348

AN:

41488

American (AMR)

AF:

0.792

AC:

12113

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.743

AC:

2577

AN:

3468

East Asian (EAS)

AF:

0.939

AC:

4872

AN:

5188

South Asian (SAS)

AF:

0.897

AC:

4329

AN:

4824

European-Finnish (FIN)

AF:

0.829

AC:

8788

AN:

10598

Middle Eastern (MID)

AF:

0.733

AC:

214

AN:

292

European-Non Finnish (NFE)

AF:

0.757

AC:

51463

AN:

68000

Other (OTH)

AF:

0.757

AC:

1594

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1315

2630

3945

5260

6575

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

870

1740

2610

3480

4350

<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:

0.772

Hom.:

16992

Bravo

AF:

0.773

Asia WGS

AF:

0.914

AC:

3178

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not provided

Benign:2

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

- -

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

-0.92

CADD

Benign

0.023

(source)

DANN

Benign

0.31

PhyloP100

-1.5

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