Variant chr8-60841790-C-T 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.4644+36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,608,036 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 8 hom. )

Consequence

CHD7
NM_017780.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.505

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=-0.86).

BP6

Variant 8-60841790-C-T is Benign according to our data. Variant chr8-60841790-C-T is described in ClinVar as [Benign]. Clinvar id is 260905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00178 (2586/1455728) while in subpopulation MID AF= 0.00486 (28/5758). AF 95% confidence interval is 0.00346. There are 8 homozygotes in gnomad4_exome. There are 1318 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High AC in GnomAd4 at 248 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD7	NM_017780.4 linkuse as main transcript	c.4644+36C>T		intron_variant		ENST00000423902.7	NP_060250.2	Q9P2D1-1Q6ZWF9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CHD7	ENST00000423902.7 linkuse as main transcript	c.4644+36C>T	intron_variant	5	NM_017780.4	ENSP00000392028.1	Q9P2D1-1
CHD7	ENST00000524602.5 linkuse as main transcript	c.1717-20439C>T	intron_variant	1		ENSP00000437061.1	Q9P2D1-4
CHD7	ENST00000695853.1 linkuse as main transcript	n.4644+36C>T	intron_variant			ENSP00000512218.1	A0A8Q3WKT9

Frequencies

GnomAD3 genomes

AF:

0.00164

AC:

249

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00240

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00214

AC:

530

AN:

248084

Hom.:

AF XY:

0.00224

AC XY:

302

AN XY:

134590

show subpopulations

Gnomad AFR exome

AF:

0.000453

Gnomad AMR exome

AF:

0.00210

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.0000560

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.00205

Gnomad NFE exome

AF:

0.00300

Gnomad OTH exome

AF:

0.00216

GnomAD4 exome

AF:

0.00178

AC:

2586

AN:

1455728

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

1318

AN XY:

723794

show subpopulations

Gnomad4 AFR exome

AF:

0.000420

Gnomad4 AMR exome

AF:

0.00222

Gnomad4 ASJ exome

AF:

0.00157

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00120

Gnomad4 FIN exome

AF:

0.00171

Gnomad4 NFE exome

AF:

0.00188

Gnomad4 OTH exome

AF:

0.00208

GnomAD4 genome

AF:

0.00163

AC:

248

AN:

152308

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

108

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00240

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000934

Hom.:

Bravo

AF:

0.00167

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.44

DANN

Benign

0.55

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