Variant 8-60852279-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_017780.4(CHD7):c.5894+32C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00803 in 1,573,018 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 17 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 61 hom. )

Consequence

CHD7
NM_017780.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.11

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=-0.85).

BP6

Variant 8-60852279-C-G is Benign according to our data. Variant chr8-60852279-C-G is described in ClinVar as [Benign]. Clinvar id is 260911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00723 (1101/152242) while in subpopulation AMR AF= 0.0133 (204/15296). AF 95% confidence interval is 0.0118. There are 17 homozygotes in gnomad4. There are 539 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1101 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD7	NM_017780.4 linkuse as main transcript	c.5894+32C>G		intron_variant		ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7 linkuse as main transcript	c.5894+32C>G	intron_variant	5	NM_017780.4	ENSP00000392028	P1	Q9P2D1-1
CHD7	ENST00000524602.5 linkuse as main transcript	c.1717-9950C>G	intron_variant	1		ENSP00000437061		Q9P2D1-4
CHD7	ENST00000695853.1 linkuse as main transcript	c.5894+32C>G	intron_variant, NMD_transcript_variant			ENSP00000512218
CHD7	ENST00000527921.1 linkuse as main transcript	n.385+32C>G	intron_variant, non_coding_transcript_variant	4

Frequencies

GnomAD3 genomes

AF:

0.00725

AC:

1103

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0134

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.0165

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00910

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00742

AC:

1737

AN:

234198

Hom.:

AF XY:

0.00728

AC XY:

930

AN XY:

127746

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.00727

Gnomad ASJ exome

AF:

0.000454

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00426

Gnomad FIN exome

AF:

0.0216

Gnomad NFE exome

AF:

0.00823

Gnomad OTH exome

AF:

0.00722

GnomAD4 exome

AF:

0.00811

AC:

11528

AN:

1420776

Hom.:

Cov.:

AF XY:

0.00792

AC XY:

5604

AN XY:

707426

show subpopulations

Gnomad4 AFR exome

AF:

0.00144

Gnomad4 AMR exome

AF:

0.00899

Gnomad4 ASJ exome

AF:

0.000478

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00441

Gnomad4 FIN exome

AF:

0.0196

Gnomad4 NFE exome

AF:

0.00859

Gnomad4 OTH exome

AF:

0.00622

GnomAD4 genome

AF:

0.00723

AC:

1101

AN:

152242

Hom.:

Cov.:

AF XY:

0.00724

AC XY:

539

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.0165

Gnomad4 NFE

AF:

0.00907

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00313

Hom.:

Bravo

AF:

0.00555

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Feb 17, 2017	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.22

DANN

Benign

0.61

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