Variant rs79276682 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.2614-48C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 1,246,588 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 25 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 34 hom. )

Consequence

CHD7
NM_017780.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.22

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=-0.83).

BP6

Variant 8-60819959-C-G is Benign according to our data. Variant chr8-60819959-C-G is described in ClinVar as [Benign]. Clinvar id is 260897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0113 (1721/152198) while in subpopulation AFR AF= 0.0391 (1625/41538). AF 95% confidence interval is 0.0375. There are 25 homozygotes in gnomad4. There are 832 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1721 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD7	NM_017780.4 linkuse as main transcript	c.2614-48C>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.2614-48C>G	intron_variant	5	NM_017780.4	ENSP00000392028	P1	Q9P2D1-1
CHD7	ENST00000524602.5 linkuse as main transcript	c.1716+38909C>G	intron_variant	1		ENSP00000437061		Q9P2D1-4
CHD7	ENST00000525508.1 linkuse as main transcript	c.2614-48C>G	intron_variant	5		ENSP00000436027		Q9P2D1-2
CHD7	ENST00000695853.1 linkuse as main transcript	c.2614-48C>G	intron_variant, NMD_transcript_variant			ENSP00000512218

Frequencies

GnomAD3 genomes

AF:

0.0112

AC:

1710

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0389

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00498

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00242

AC:

393

AN:

162152

Hom.:

AF XY:

0.00185

AC XY:

159

AN XY:

85936

show subpopulations

Gnomad AFR exome

AF:

0.0378

Gnomad AMR exome

AF:

0.00214

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000887

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000135

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00128

AC:

1403

AN:

1094390

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

603

AN XY:

554236

show subpopulations

Gnomad4 AFR exome

AF:

0.0413

Gnomad4 AMR exome

AF:

0.00252

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000688

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000110

Gnomad4 OTH exome

AF:

0.00282

GnomAD4 genome

AF:

0.0113

AC:

1721

AN:

152198

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

832

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0391

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00584

Hom.:

Bravo

AF:

0.0129

Asia WGS

AF:

0.00404

AC:

AN:

3478

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

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.8

DANN

Benign

0.56

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