5-98856619-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001270.4(CHD1):c.4894C>G(p.Arg1632Gly) variant causes a missense change involving the alteration of a 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 (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHD1 NM_001270.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.21

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, CHD1
• BP4: Computational evidence support a benign effect (MetaRNN=0.20166907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD1	NM_001270.4	c.4894C>G	p.Arg1632Gly	missense_variant	36/36	ENST00000614616.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD1	ENST00000614616.5	c.4894C>G	p.Arg1632Gly	missense_variant	36/36	5	NM_001270.4	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Pilarowski-Bjornsson syndrome Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare

Dec 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.075	T;T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Uncertain	0.047	D
MutationAssessor	Uncertain	2.4	M;M
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.39	T
Sift4G	Benign	0.076	T;T
Polyphen		0.0	B;B
Vest4		0.24
MutPred		0.28		Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);
MVP		0.78
MPC		0.043
ClinPred		0.92	D
GERP RS		5.5
Varity_R		0.16
gMVP		0.46

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

Other links and lift over

dbSNP: rs374564623; hg19: chr5-98192323;