Genetic Variant CHD1:p.Arg1644Leu (chr5-98856582-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001270.4(CHD1):c.4931G>T(p.Arg1644Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1644G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

CHD1
NM_001270.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.74

Publications

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

CHD1 links:

ENSG00000295348 (HGNC:):

ENSG00000295348 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.4931G>T	p.Arg1644Leu	missense	Exon 36 of 36	NP_001261.2	O14646-1
CHD1	NM_001364113.3		c.5195G>T	p.Arg1732Leu	missense	Exon 37 of 37	NP_001351042.1	A0A087WVF4
CHD1	NM_001376194.2		c.4931G>T	p.Arg1644Leu	missense	Exon 36 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.4931G>T	p.Arg1644Leu	missense	Exon 36 of 36	ENSP00000483667.1	O14646-1
CHD1	ENST00000511067.3	TSL:5	c.5195G>T	p.Arg1732Leu	missense	Exon 37 of 37	ENSP00000479403.2	A0A087WVF4
CHD1	ENST00000926040.1		c.4931G>T	p.Arg1644Leu	missense	Exon 36 of 36	ENSP00000596099.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251154

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000165

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.056

MetaRNN

Uncertain

0.50

MetaSVM

Uncertain

0.72

MutationAssessor

Benign

0.34

PhyloP100

5.7

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.51

Sift

Uncertain

0.0070

Sift4G

Benign

0.30

Polyphen

0.99

Vest4

0.52

MutPred

0.19

Loss of MoRF binding (P = 0.0275)

MVP

0.87

MPC

0.046

ClinPred

0.81

GERP RS

5.5

Varity_R

0.21

gMVP

0.56

Mutation Taster

=70/30

polymorphism

(source)

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

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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