Variant 5-98897307-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP5

The NM_001270.4(CHD1):c.1379G>A(p.Arg460Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,012 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

CHD1
NM_001270.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.54

Variant links:

Genes affected

CHD1 (HGNC:1915): (chromodomain helicase DNA binding protein 1) The CHD family of proteins is characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. CHD genes alter gene expression possibly by modification of chromatin structure thus altering access of the transcriptional apparatus to its chromosomal DNA template. [provided by RefSeq, Jul 2008]

CHD1 links:

CHD1 (HGNC:):

CHD1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CHD1. . Trascript score misZ 3.2778 (greater than threshold 3.09). GenCC has associacion of gene with Pilarowski-Bjornsson syndrome.

PP5

Variant 5-98897307-C-T is Pathogenic according to our data. Variant chr5-98897307-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 438821.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD1	NM_001270.4 linkuse as main transcript	c.1379G>A	p.Arg460Lys	missense_variant	11/36	ENST00000614616.5	NP_001261.2	O14646-1B3KT33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CHD1	ENST00000614616.5 linkuse as main transcript	c.1379G>A	p.Arg460Lys	missense_variant	11/36	5	NM_001270.4	ENSP00000483667.1	O14646-1
CHD1	ENST00000511067.3 linkuse as main transcript	c.1379G>A	p.Arg460Lys	missense_variant	11/37	5		ENSP00000479403.2	A0A087WVF4
CHD1	ENST00000706140.1 linkuse as main transcript	n.1526G>A		non_coding_transcript_exon_variant	10/34
CHD1	ENST00000706141.1 linkuse as main transcript	n.1379G>A		non_coding_transcript_exon_variant	11/37			ENSP00000516225.1	A0A994J7K7

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152012

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Pilarowski-Bjornsson syndrome

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

T;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

.;D

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Uncertain

0.68

MutationAssessor

Uncertain

2.5

M;M

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-2.7

.;D

REVEL

Uncertain

0.58

Sift

Benign

0.13

.;T

Sift4G

Uncertain

0.015

D;D

Polyphen

0.56

P;P

Vest4

0.58

MutPred

0.43

Gain of methylation at R460 (P = 0.017);Gain of methylation at R460 (P = 0.017);

MVP

0.90

MPC

1.7

ClinPred

0.98

GERP RS

5.7

Varity_R

0.31

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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