dbSNP rs7844902: CHD7:c.4533+46A>G (chr8-60838301-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).

BP6

Variant 8-60838301-A-G is Benign according to our data. Variant chr8-60838301-A-G is described in ClinVar as [Benign]. Clinvar id 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	Q9P2D1-1Q6ZWF9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHD7	ENST00000423902.7 link	c.4533+46A>G	intron_variant	Intron 19 of 37	5	NM_017780.4	ENSP00000392028.1	Q9P2D1-1
CHD7	ENST00000524602.5 link	c.1717-23928A>G	intron_variant	Intron 2 of 4	1		ENSP00000437061.1	Q9P2D1-4
CHD7	ENST00000695853.1 link	n.4533+46A>G	intron_variant	Intron 19 of 36			ENSP00000512218.1	A0A8Q3WKT9

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

GnomAD3 exomes

AF:

0.804

AC:

148968

AN:

185184

Hom.:

60234

AF XY:

0.807

AC XY:

79047

AN XY:

97980

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 SAS exome

AF:

0.890

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

Gnomad4 AFR exome

AF:

0.784

Gnomad4 AMR exome

AF:

0.808

Gnomad4 ASJ exome

AF:

0.755

Gnomad4 EAS exome

AF:

0.938

Gnomad4 SAS exome

AF:

0.889

Gnomad4 FIN exome

AF:

0.833

Gnomad4 NFE exome

AF:

0.746

Gnomad4 OTH exome

AF:

0.779

GnomAD4 genome

AF:

0.782

AC:

118938

AN:

152168

Hom.:

46707

Cov.:

AF XY:

0.790

AC XY:

58806

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.780

Gnomad4 AMR

AF:

0.792

Gnomad4 ASJ

AF:

0.743

Gnomad4 EAS

AF:

0.939

Gnomad4 SAS

AF:

0.897

Gnomad4 FIN

AF:

0.829

Gnomad4 NFE

AF:

0.757

Gnomad4 OTH

AF:

0.757

Alfa

AF:

0.764

Hom.:

9058

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

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

- -

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

DANN

Benign

0.31

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