1-226368742-A-T

Variant names:

• chr1-226368742-A-T
• rs3219119
• NM_001618.4:c.2155-421T>A

Variant summary

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

The NM_001618.4(PARP1):​c.2155-421T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 149,478 control chromosomes in the GnomAD database, including 24,186 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 0.55 (24186 hom., cov: 33)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.584
• Publications: 16 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.665 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP1	NM_001618.4	MANE Select	c.2155-421T>A		intron	N/A	NP_001609.2	P09874

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP1	ENST00000366794.10	TSL:1 MANE Select	c.2155-421T>A		intron	N/A	ENSP00000355759.5	P09874
	PARP1	ENST00000922077.1		c.2149-421T>A		intron	N/A	ENSP00000592136.1
	PARP1	ENST00000922078.1		c.2149-421T>A		intron	N/A	ENSP00000592137.1

Frequencies

GnomAD3 genomes AF: 0.551 AC: 82349 AN: 149366 Hom.: 24192 Cov.: 33

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.551 AC: 82369 AN: 149478 Hom.: 24186 Cov.: 33 AF XY: 0.548 AC XY: 39983 AN XY: 73008

African (AFR) AF: 0.354 AC: 13809 AN: 39002

American (AMR) AF: 0.533 AC: 8076 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2398 AN: 3466

East Asian (EAS) AF: 0.194 AC: 1005 AN: 5184

South Asian (SAS) AF: 0.626 AC: 3021 AN: 4824

European-Finnish (FIN) AF: 0.600 AC: 6353 AN: 10580

Middle Eastern (MID) AF: 0.675 AC: 197 AN: 292

European-Non Finnish (NFE) AF: 0.670 AC: 45558 AN: 67960

Other (OTH) AF: 0.590 AC: 1237 AN: 2096

Alfa AF: 0.489 Hom.: 1528

Bravo AF: 0.522

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.69
PhyloP100		-0.58
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: rs3219119; hg19: chr1-226556443; COSMIC: COSV64689701; COSMIC: COSV64689701;