Variant 12-6578867-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BS2

The NM_001273.5(CHD4):c.4960C>A(p.Pro1654Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CHD4
NM_001273.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.08

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, CHD4

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CHD4	NM_001273.5 linkuse as main transcript	c.4960C>A	p.Pro1654Thr	missense_variant	34/40	ENST00000544040.7
CHD4	NM_001297553.2 linkuse as main transcript	c.4939C>A	p.Pro1647Thr	missense_variant	33/39
CHD4	NM_001363606.2 linkuse as main transcript	c.4927C>A	p.Pro1643Thr	missense_variant	34/40

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD4	ENST00000544040.7 linkuse as main transcript	c.4960C>A	p.Pro1654Thr	missense_variant	34/40	5	NM_001273.5	A1	Q14839-1
	ENST00000501075.2 linkuse as main transcript	n.100+146G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251460

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2017

Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Uncertain

0.090

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

DANN

Uncertain

0.98

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

T;T;T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.49

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.48

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.70

REVEL

Uncertain

0.56

Polyphen

1.0, 1.0

.;.;D;D;.;.;.;.;D;.;.

Vest4

0.57

MutPred

0.32

.;.;.;Gain of sheet (P = 0.0221);.;.;.;.;.;.;.;

MVP

0.76

MPC

0.043

ClinPred

0.31

GERP RS

5.7

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

Varity_R

0.12

gMVP

0.41

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