rs3219110

Positions:

• chr1-226370177-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000366794.10(PARP1):​c.2154+257A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,812 control chromosomes in the GnomAD database, including 11,927 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 0.39 (11927 hom., cov: 30)
• Consequence: PARP1 ENST00000366794.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP1	NM_001618.4	c.2154+257A>G		intron_variant		ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10	c.2154+257A>G		intron_variant		1	NM_001618.4	ENSP00000355759	P1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 58967 AN: 151694 Hom.: 11926 Cov.: 30

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.389 AC: 58994 AN: 151812 Hom.: 11927 Cov.: 30 AF XY: 0.390 AC XY: 28949 AN XY: 74162

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.399

Alfa AF: 0.449 Hom.: 16140

Bravo AF: 0.373

Asia WGS AF: 0.309 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs3219110; hg19: chr1-226557878; COSMIC: COSV64689710;