5-98868016-A-G

Variant names:

• chr5-98868016-A-G
• rs161942
• NM_001270.4:c.4248+479T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001270.4(CHD1):​c.4248+479T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,290 control chromosomes in the GnomAD database, including 10,004 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (10004 hom., cov: 28)
• Consequence: CHD1 NM_001270.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.847
• Publications: 12 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

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.4248+479T>C		intron	N/A	NP_001261.2
	CHD1	NM_001364113.3		c.4512+479T>C		intron	N/A	NP_001351042.1
	CHD1	NM_001376194.2		c.4248+479T>C		intron	N/A	NP_001363123.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD1	ENST00000614616.5	TSL:5 MANE Select	c.4248+479T>C		intron	N/A	ENSP00000483667.1
	CHD1	ENST00000511067.3	TSL:5	c.4512+479T>C		intron	N/A	ENSP00000479403.2
	CHD1	ENST00000505657.1	TSL:3	n.135+479T>C		intron	N/A	ENSP00000422225.1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50269 AN: 151174 Hom.: 9993 Cov.: 28

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.0523

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.333 AC: 50312 AN: 151290 Hom.: 10004 Cov.: 28 AF XY: 0.321 AC XY: 23730 AN XY: 73896

African (AFR) AF: 0.551 AC: 22697 AN: 41190

American (AMR) AF: 0.233 AC: 3545 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3468

East Asian (EAS) AF: 0.0522 AC: 268 AN: 5130

South Asian (SAS) AF: 0.191 AC: 913 AN: 4776

European-Finnish (FIN) AF: 0.151 AC: 1578 AN: 10446

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19018 AN: 67760

Other (OTH) AF: 0.316 AC: 666 AN: 2108

Alfa AF: 0.311 Hom.: 1097

Bravo AF: 0.351

Asia WGS AF: 0.156 AC: 541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.1
DANN	Benign	0.65
PhyloP100		-0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs161942; hg19: chr5-98203720;