NM_001270.4:c.4976_4977delGGinsCC

Variant names:

• chr5-98856536-CC-GG
• NM_001270.4:c.4976_4977delGGinsCC
• CHD1 p.Arg1659Thr

Variant summary

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

The NM_001270.4(CHD1):​c.4976_4977delGGinsCC​(p.Arg1659Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHD1 NM_001270.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.16
• Publications: 0 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• complex neurodevelopmental disorder

  Inheritance: AR, AD Classification: LIMITED Submitted by: Ambry Genetics, ClinGen

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD1	NM_001270.4	MANE Select	c.4976_4977delGGinsCC	p.Arg1659Thr	missense	N/A	NP_001261.2	O14646-1
	CHD1	NM_001364113.3		c.5240_5241delGGinsCC	p.Arg1747Thr	missense	N/A	NP_001351042.1	A0A087WVF4
	CHD1	NM_001376194.2		c.4976_4977delGGinsCC	p.Arg1659Thr	missense	N/A	NP_001363123.1	O14646-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD1	ENST00000614616.5	TSL:5 MANE Select	c.4976_4977delGGinsCC	p.Arg1659Thr	missense	N/A	ENSP00000483667.1	O14646-1
	CHD1	ENST00000511067.3	TSL:5	c.5240_5241delGGinsCC	p.Arg1747Thr	missense	N/A	ENSP00000479403.2	A0A087WVF4
	CHD1	ENST00000926040.1		c.4976_4977delGGinsCC	p.Arg1659Thr	missense	N/A	ENSP00000596099.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-98192240;