Variant 8-60819962-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017780.4(CHD7):c.2614-45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 1,283,818 control chromosomes in the GnomAD database, including 401,297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 48685 hom., cov: 32)

Exomes 𝑓: 0.79 ( 352612 hom. )

Consequence

CHD7
NM_017780.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.989

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=-0.84).

BP6

Variant 8-60819962-A-G is Benign according to our data. Variant chr8-60819962-A-G is described in ClinVar as [Benign]. Clinvar id is 158326.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/exons	MANE	Protein	UniProt
CHD7	NM_017780.4 link	c.2614-45A>G		intron_variant		ENST00000423902.7	NP_060250.2	Q9P2D1-1Q6ZWF9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CHD7	ENST00000423902.7 link	c.2614-45A>G	intron_variant	5	NM_017780.4	ENSP00000392028.1	Q9P2D1-1
CHD7	ENST00000524602.5 link	c.1716+38912A>G	intron_variant	1		ENSP00000437061.1	Q9P2D1-4
CHD7	ENST00000525508.1 link	c.2614-45A>G	intron_variant	5		ENSP00000436027.1	Q9P2D1-2
CHD7	ENST00000695853.1 link	n.2614-45A>G	intron_variant			ENSP00000512218.1	A0A8Q3WKT9

Frequencies

GnomAD3 genomes

AF:

0.799

AC:

121459

AN:

152036

Hom.:

48661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.800

Gnomad AMI

AF:

0.730

Gnomad AMR

AF:

0.813

Gnomad ASJ

AF:

0.762

Gnomad EAS

AF:

0.939

Gnomad SAS

AF:

0.903

Gnomad FIN

AF:

0.832

Gnomad MID

AF:

0.741

Gnomad NFE

AF:

0.775

Gnomad OTH

AF:

0.774

GnomAD3 exomes

AF:

0.817

AC:

135194

AN:

165404

Hom.:

55521

AF XY:

0.820

AC XY:

71926

AN XY:

87720

show subpopulations

Gnomad AFR exome

AF:

0.812

Gnomad AMR exome

AF:

0.827

Gnomad ASJ exome

AF:

0.765

Gnomad EAS exome

AF:

0.939

Gnomad SAS exome

AF:

0.895

Gnomad FIN exome

AF:

0.839

Gnomad NFE exome

AF:

0.772

Gnomad OTH exome

AF:

0.785

GnomAD4 exome

AF:

0.788

AC:

891354

AN:

1131664

Hom.:

352612

Cov.:

AF XY:

0.791

AC XY:

451966

AN XY:

571566

show subpopulations

Gnomad4 AFR exome

AF:

0.802

Gnomad4 AMR exome

AF:

0.824

Gnomad4 ASJ exome

AF:

0.770

Gnomad4 EAS exome

AF:

0.938

Gnomad4 SAS exome

AF:

0.895

Gnomad4 FIN exome

AF:

0.837

Gnomad4 NFE exome

AF:

0.767

Gnomad4 OTH exome

AF:

0.796

GnomAD4 genome

AF:

0.799

AC:

121537

AN:

152154

Hom.:

48685

Cov.:

AF XY:

0.807

AC XY:

60014

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.800

Gnomad4 AMR

AF:

0.813

Gnomad4 ASJ

AF:

0.762

Gnomad4 EAS

AF:

0.939

Gnomad4 SAS

AF:

0.903

Gnomad4 FIN

AF:

0.832

Gnomad4 NFE

AF:

0.775

Gnomad4 OTH

AF:

0.776

Alfa

AF:

0.761

Hom.:

6297

Bravo

AF:

0.791

Asia WGS

AF:

0.913

AC:

3173

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

CHARGE syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Hypogonadotropic hypogonadism 5 with or without anosmia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.7

DANN

Benign

0.70

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