rs1293161341

Variant names:

• chr5-98856390-C-T
• rs1293161341
• NM_001270.4:c.5123G>A

Variant summary

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

The NM_001270.4(CHD1):​c.5123G>A​(p.Arg1708Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000413 in 1,454,384 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1708W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CHD1 NM_001270.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1
• Conservation: PhyloP100: 7.10
• Publications: 3 publications found

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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000295348 (HGNC:):

ACMG classification

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

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD1	NM_001270.4	MANE Select	c.5123G>A	p.Arg1708Gln	missense	Exon 36 of 36	NP_001261.2
	CHD1	NM_001364113.3		c.5387G>A	p.Arg1796Gln	missense	Exon 37 of 37	NP_001351042.1
	CHD1	NM_001376194.2		c.5123G>A	p.Arg1708Gln	missense	Exon 36 of 36	NP_001363123.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD1	ENST00000614616.5	TSL:5 MANE Select	c.5123G>A	p.Arg1708Gln	missense	Exon 36 of 36	ENSP00000483667.1
	CHD1	ENST00000511067.3	TSL:5	c.5387G>A	p.Arg1796Gln	missense	Exon 37 of 37	ENSP00000479403.2
	CHD1	ENST00000512392.5	TSL:2	n.1310G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000413 AC: 6 AN: 1454384 Hom.: 0 Cov.: 30 AF XY: 0.00000692 AC XY: 5 AN XY: 722212

African (AFR) AF: 0.0000301 AC: 1 AN: 33276

American (AMR) AF: 0.00 AC: 0 AN: 44466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25968

East Asian (EAS) AF: 0.00 AC: 0 AN: 39526

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1105874

Other (OTH) AF: 0.00 AC: 0 AN: 60098

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
1	-	-	Pilarowski-Bjornsson syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.18	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	0.76	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.64
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.049	D
Polyphen		0.99	D
Vest4		0.54
MVP		0.82
MPC		0.047
ClinPred		0.86	D
GERP RS		5.5
Varity_R		0.12
gMVP		0.64
Mutation Taster		=13/87	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs1293161341; hg19: chr5-98192094;