Variant 12-6570710-G-A 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_001273.5(CHD4):c.5722-17C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00445 in 1,614,098 control chromosomes in the GnomAD database, including 146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 42 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 104 hom. )

Consequence

CHD4
NM_001273.5 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0730

Variant links:

Genes affected

CHD4 (HGNC:1919): (chromodomain helicase DNA binding protein 4) The product of this gene belongs to the SNF2/RAD54 helicase family. It represents the main component of the nucleosome remodeling and deacetylase complex and plays an important role in epigenetic transcriptional repression. Patients with dermatomyositis develop antibodies against this protein. Somatic mutations in this gene are associated with serous endometrial tumors. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]

CHD4 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=-0.98).

BP6

Variant 12-6570710-G-A is Benign according to our data. Variant chr12-6570710-G-A is described in ClinVar as [Benign]. Clinvar id is 1605705.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 = 0.0131 (1995/152230) while in subpopulation AFR AF= 0.0401 (1667/41532). AF 95% confidence interval is 0.0385. There are 42 homozygotes in gnomad4. There are 975 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1995 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CHD4	NM_001273.5 linkuse as main transcript	c.5722-17C>T	splice_polypyrimidine_tract_variant, intron_variant	ENST00000544040.7
CHD4	NM_001297553.2 linkuse as main transcript	c.5701-17C>T	splice_polypyrimidine_tract_variant, intron_variant
CHD4	NM_001363606.2 linkuse as main transcript	c.5692-17C>T	splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD4	ENST00000544040.7 linkuse as main transcript	c.5722-17C>T		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001273.5	A1	Q14839-1

Frequencies

GnomAD3 genomes

AF:

0.0131

AC:

1994

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0403

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0133

Gnomad SAS

AF:

0.0307

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.00825

AC:

2061

AN:

249758

Hom.:

AF XY:

0.00870

AC XY:

1176

AN XY:

135152

show subpopulations

Gnomad AFR exome

AF:

0.0419

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.0156

Gnomad SAS exome

AF:

0.0320

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000330

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00355

AC:

5192

AN:

1461868

Hom.:

104

Cov.:

AF XY:

0.00428

AC XY:

3111

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0414

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.00180

Gnomad4 EAS exome

AF:

0.0134

Gnomad4 SAS exome

AF:

0.0296

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000221

Gnomad4 OTH exome

AF:

0.00527

GnomAD4 genome

AF:

0.0131

AC:

1995

AN:

152230

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

975

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0401

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.0137

Gnomad4 SAS

AF:

0.0309

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00996

Alfa

AF:

0.00255

Hom.:

Bravo

AF:

0.0137

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -
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

-0.98

CADD

Benign

9.9

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