chr5-98856633-G-A

Variant names:

• chr5-98856633-G-A
• rs1748055031
• NM_001270.4:c.4880C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001270.4(CHD1):​c.4880C>T​(p.Ser1627Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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: 1.67
• 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: 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

ENSG00000295348 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0812515).

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.4880C>T	p.Ser1627Phe	missense	Exon 36 of 36	NP_001261.2	O14646-1
	CHD1	NM_001364113.3		c.5144C>T	p.Ser1715Phe	missense	Exon 37 of 37	NP_001351042.1	A0A087WVF4
	CHD1	NM_001376194.2		c.4880C>T	p.Ser1627Phe	missense	Exon 36 of 36	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.4880C>T	p.Ser1627Phe	missense	Exon 36 of 36	ENSP00000483667.1	O14646-1
	CHD1	ENST00000511067.3	TSL:5	c.5144C>T	p.Ser1715Phe	missense	Exon 37 of 37	ENSP00000479403.2	A0A087WVF4
	CHD1	ENST00000926040.1		c.4880C>T	p.Ser1627Phe	missense	Exon 36 of 36	ENSP00000596099.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Benign	0.59
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.086
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.25
Sift	Benign	0.71	T
Sift4G	Benign	0.12	T
Polyphen		0.011	B
Vest4		0.17
MutPred		0.16		Loss of phosphorylation at S1627 (P = 0.0026)
MVP		0.61
MPC		0.039
ClinPred		0.13	T
GERP RS		3.7
Varity_R		0.053
gMVP		0.32
Mutation Taster		=86/14	polymorphism

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: rs1748055031; hg19: chr5-98192337;