1-226381674-G-C

Variant names:

• chr1-226381674-G-C
• rs3219073
• NM_001618.4:c.1160-466C>G

Variant summary

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

The NM_001618.4(PARP1):​c.1160-466C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,170 control chromosomes in the GnomAD database, including 4,632 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 0.23 (4632 hom., cov: 33)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 13 publications found

Genes affected

PARP1 (HGNC:270): (poly(ADP-ribose) polymerase 1) This gene encodes a chromatin-associated enzyme, poly(ADP-ribosyl)transferase, which modifies various nuclear proteins by poly(ADP-ribosyl)ation. The modification is dependent on DNA and is involved in the regulation of various important cellular processes such as differentiation, proliferation, and tumor transformation and also in the regulation of the molecular events involved in the recovery of cell from DNA damage. In addition, this enzyme may be the site of mutation in Fanconi anemia, and may participate in the pathophysiology of type I diabetes. [provided by RefSeq, Jul 2008]

PARP1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

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 = 0.36 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001618.4. 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
	PARP1	NM_001618.4	MANE Select	c.1160-466C>G		intron	N/A	NP_001609.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP1	ENST00000366794.10	TSL:1 MANE Select	c.1160-466C>G		intron	N/A	ENSP00000355759.5
	PARP1	ENST00000922077.1		c.1154-466C>G		intron	N/A	ENSP00000592136.1
	PARP1	ENST00000922078.1		c.1154-466C>G		intron	N/A	ENSP00000592137.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34247 AN: 152052 Hom.: 4629 Cov.: 33

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.225 AC: 34272 AN: 152170 Hom.: 4632 Cov.: 33 AF XY: 0.224 AC XY: 16631 AN XY: 74398

African (AFR) AF: 0.365 AC: 15138 AN: 41482

American (AMR) AF: 0.143 AC: 2188 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 481 AN: 3468

East Asian (EAS) AF: 0.338 AC: 1745 AN: 5166

South Asian (SAS) AF: 0.176 AC: 850 AN: 4828

European-Finnish (FIN) AF: 0.166 AC: 1759 AN: 10600

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11503 AN: 68012

Other (OTH) AF: 0.201 AC: 424 AN: 2108

Alfa AF: 0.0978 Hom.: 145

Bravo AF: 0.233

Asia WGS AF: 0.243 AC: 844 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	0.021
DANN	Benign	0.41
PhyloP100		-1.6
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: rs3219073; hg19: chr1-226569375;