Variant 8-60678877-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_017780.4(CHD7):c.-380C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 150,674 control chromosomes in the GnomAD database, including 1,329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1313 hom., cov: 30)

Exomes 𝑓: 0.17 ( 16 hom. )

Consequence

CHD7
NM_017780.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.818

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:

CHD7 (HGNC:):

CHD7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 8-60678877-C-T is Benign according to our data. Variant chr8-60678877-C-T is described in ClinVar as [Benign]. Clinvar id is 363434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-60678877-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD7	NM_017780.4 linkuse as main transcript	c.-380C>T		5_prime_UTR_premature_start_codon_gain_variant	1/38	ENST00000423902.7	NP_060250.2	Q9P2D1-1Q6ZWF9
CHD7	NM_017780.4 linkuse as main transcript	c.-380C>T		5_prime_UTR_variant	1/38	ENST00000423902.7	NP_060250.2	Q9P2D1-1Q6ZWF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902 linkuse as main transcript	c.-380C>T		5_prime_UTR_premature_start_codon_gain_variant	1/38	5	NM_017780.4	ENSP00000392028.1		Q9P2D1-1
CHD7	ENST00000423902 linkuse as main transcript	c.-380C>T		5_prime_UTR_variant	1/38	5	NM_017780.4	ENSP00000392028.1		Q9P2D1-1

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

16860

AN:

149514

Hom.:

1312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0250

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.308

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.106

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.110

GnomAD4 exome

AF:

0.167

AC:

181

AN:

1084

Hom.:

Cov.:

AF XY:

0.184

AC XY:

101

AN XY:

550

show subpopulations

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.167

Gnomad4 SAS exome

AF:

0.185

Gnomad4 FIN exome

AF:

0.0556

Gnomad4 NFE exome

AF:

0.121

Gnomad4 OTH exome

AF:

0.154

GnomAD4 genome

AF:

0.113

AC:

16852

AN:

149590

Hom.:

1313

Cov.:

AF XY:

0.115

AC XY:

8415

AN XY:

73004

show subpopulations

Gnomad4 AFR

AF:

0.0249

Gnomad4 AMR

AF:

0.102

Gnomad4 ASJ

AF:

0.121

Gnomad4 EAS

AF:

0.309

Gnomad4 SAS

AF:

0.197

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.144

Gnomad4 OTH

AF:

0.109

Alfa

AF:

0.0963

Hom.:

196

Bravo

AF:

0.105

Asia WGS

AF:

0.237

AC:

815

AN:

3454

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hypogonadotropic hypogonadism 5 with or without anosmia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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