dbSNP rs5891777: CHD7:c.2376+43_2376+48dupTGGACT (chr8-60800567-A-ATGGACT) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_017780.4(CHD7):c.2376+43_2376+48dupTGGACT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 1,550,796 control chromosomes in the GnomAD database, including 469,561 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 45749 hom., cov: 0)

Exomes 𝑓: 0.78 ( 423812 hom. )

Consequence

CHD7
NM_017780.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.541

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 was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 8-60800567-A-ATGGACT is Benign according to our data. Variant chr8-60800567-A-ATGGACT is described in ClinVar as [Likely_benign]. Clinvar id is 260894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4 link	c.2376+43_2376+48dupTGGACT		intron_variant	Intron 5 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.2376+42_2376+43insTGGACT		intron_variant	Intron 5 of 37	5	NM_017780.4	ENSP00000392028.1		Q9P2D1-1

Frequencies

GnomAD3 genomes

AF:

0.776

AC:

117300

AN:

151208

Hom.:

45725

Cov.:

show subpopulations

Gnomad AFR

AF:

0.729

Gnomad AMI

AF:

0.725

Gnomad AMR

AF:

0.806

Gnomad ASJ

AF:

0.746

Gnomad EAS

AF:

0.943

Gnomad SAS

AF:

0.875

Gnomad FIN

AF:

0.831

Gnomad MID

AF:

0.732

Gnomad NFE

AF:

0.772

Gnomad OTH

AF:

0.754

GnomAD2 exomes

AF:

0.801

AC:

166321

AN:

207726

AF XY:

0.802

show subpopulations

Gnomad AFR exome

AF:

0.732

Gnomad AMR exome

AF:

0.820

Gnomad ASJ exome

AF:

0.748

Gnomad EAS exome

AF:

0.939

Gnomad FIN exome

AF:

0.837

Gnomad NFE exome

AF:

0.765

Gnomad OTH exome

AF:

0.782

GnomAD4 exome

AF:

0.776

AC:

1085308

AN:

1399472

Hom.:

423812

Cov.:

AF XY:

0.778

AC XY:

537772

AN XY:

691640

show subpopulations

Gnomad4 AFR exome

AF:

0.731

AC:

23041

AN:

31518

Gnomad4 AMR exome

AF:

0.819

AC:

31192

AN:

38066

Gnomad4 ASJ exome

AF:

0.755

AC:

17640

AN:

23354

Gnomad4 EAS exome

AF:

0.949

AC:

36662

AN:

38632

Gnomad4 SAS exome

AF:

0.864

AC:

66138

AN:

76578

Gnomad4 FIN exome

AF:

0.835

AC:

43021

AN:

51516

Gnomad4 NFE exome

AF:

0.760

AC:

818289

AN:

1076526

Gnomad4 Remaining exome

AF:

0.783

AC:

45248

AN:

57786

Heterozygous variant carriers

11117

22234

33352

44469

55586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

20116

40232

60348

80464

100580

<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:

0.776

AC:

117374

AN:

151324

Hom.:

45749

Cov.:

AF XY:

0.784

AC XY:

57925

AN XY:

73918

show subpopulations

Gnomad4 AFR

AF:

0.729

AC:

0.729047

AN:

0.729047

Gnomad4 AMR

AF:

0.805

AC:

0.805457

AN:

0.805457

Gnomad4 ASJ

AF:

0.746

AC:

0.746385

AN:

0.746385

Gnomad4 EAS

AF:

0.943

AC:

0.942562

AN:

0.942562

Gnomad4 SAS

AF:

0.875

AC:

0.87526

AN:

0.87526

Gnomad4 FIN

AF:

0.831

AC:

0.830568

AN:

0.830568

Gnomad4 NFE

AF:

0.772

AC:

0.772001

AN:

0.772001

Gnomad4 OTH

AF:

0.756

AC:

0.755714

AN:

0.755714

Heterozygous variant carriers

1321

2642

3964

5285

6606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

860

1720

2580

3440

4300

<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:

0.762

Hom.:

9294

Asia WGS

AF:

0.900

AC:

3129

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely 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

- -

not provided

Benign:1

Jun 16, 2018

GeneDx

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

Mutation Taster

=100/0

polymorphism (auto)

Splicing

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