Genetic Variant CHD1:p.Arg141Gly (chr5-98902916-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001270.4(CHD1):c.421A>G(p.Arg141Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CHD1
NM_001270.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 2.24

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

Pilarowski-Bjornsson syndrome
Inheritance: AD, Unknown Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
complex neurodevelopmental disorder
Inheritance: AR, AD Classification: LIMITED Submitted by: Ambry Genetics, ClinGen

CHD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17300662).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHD1	NM_001270.4	MANE Select	c.421A>G	p.Arg141Gly	missense	Exon 5 of 36	NP_001261.2	O14646-1
CHD1	NM_001364113.3		c.421A>G	p.Arg141Gly	missense	Exon 5 of 37	NP_001351042.1	A0A087WVF4
CHD1	NM_001376194.2		c.421A>G	p.Arg141Gly	missense	Exon 5 of 36	NP_001363123.1	O14646-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHD1	ENST00000614616.5	TSL:5 MANE Select	c.421A>G	p.Arg141Gly	missense	Exon 5 of 36	ENSP00000483667.1	O14646-1
CHD1	ENST00000511067.3	TSL:5	c.421A>G	p.Arg141Gly	missense	Exon 5 of 37	ENSP00000479403.2	A0A087WVF4
CHD1	ENST00000926040.1		c.421A>G	p.Arg141Gly	missense	Exon 5 of 36	ENSP00000596099.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1451318

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722506

African (AFR)

AF:

0.00

AC:

AN:

33202

American (AMR)

AF:

0.00

AC:

AN:

44398

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25990

East Asian (EAS)

AF:

0.00

AC:

AN:

39430

South Asian (SAS)

AF:

0.00

AC:

AN:

85616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5618

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1104718

Other (OTH)

AF:

0.00

AC:

AN:

60050

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Pilarowski-Bjornsson syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

Eigen

Benign

-0.14

Eigen_PC

Benign

0.036

FATHMM_MKL

Benign

0.39

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.045

MetaRNN

Benign

0.17

MetaSVM

Uncertain

-0.070

MutationAssessor

Benign

1.5

PhyloP100

2.2

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.31

Sift

Uncertain

0.0040

Sift4G

Benign

0.15

Polyphen

0.079

Vest4

0.26

MutPred

0.38

Loss of stability (P = 0.0086)

MVP

0.73

MPC

0.15

ClinPred

0.82

GERP RS

4.8

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.0

Varity_R

0.21

gMVP

0.28

Mutation Taster

=22/78

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over