5-98856663-G-A

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.4850C>T(p.Ser1617Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHD1 NM_001270.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.62

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=0.07962564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD1	NM_001270.4	c.4850C>T	p.Ser1617Leu	missense_variant	36/36	ENST00000614616.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD1	ENST00000614616.5	c.4850C>T	p.Ser1617Leu	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: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Dec 08, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	22
Dann	Uncertain	0.98
DEOGEN2	Benign	0.072	T;T
Eigen	Benign	0.019
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.080	T;T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	0.81	L;L
MutationTaster	Benign	0.98	D
PrimateAI	Benign	0.44	T
Sift4G	Benign	0.34	T;T
Polyphen		0.0	B;B
Vest4		0.078
MutPred		0.18		Loss of phosphorylation at S1617 (P = 0.0054);Loss of phosphorylation at S1617 (P = 0.0054);
MVP		0.52
MPC		0.034
ClinPred		0.79	D
GERP RS		5.5
Varity_R		0.11
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-98192367;