rs2117114

Variant names:

• chr1-226383918-G-A
• rs2117114
• NM_001618.4:c.1012-735C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-226383918-G-A
• chr1-226383918-G-C

Variant summary

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

The NM_001618.4(PARP1):​c.1012-735C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,190 control chromosomes in the GnomAD database, including 51,256 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 0.82 (51256 hom., cov: 33)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• Publications: 9 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

ENSG00000295046 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP1	NM_001618.4	c.1012-735C>T		intron_variant	Intron 7 of 22	ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10	c.1012-735C>T		intron_variant	Intron 7 of 22	1	NM_001618.4	ENSP00000355759.5

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124184 AN: 152072 Hom.: 51244 Cov.: 33

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.820

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

GnomAD4 genome AF: 0.816 AC: 124243 AN: 152190 Hom.: 51256 Cov.: 33 AF XY: 0.810 AC XY: 60304 AN XY: 74420

African (AFR) AF: 0.869 AC: 36088 AN: 41536

American (AMR) AF: 0.690 AC: 10545 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2887 AN: 3470

East Asian (EAS) AF: 0.532 AC: 2754 AN: 5172

South Asian (SAS) AF: 0.803 AC: 3877 AN: 4826

European-Finnish (FIN) AF: 0.767 AC: 8116 AN: 10580

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57152 AN: 68008

Other (OTH) AF: 0.817 AC: 1723 AN: 2108

Alfa AF: 0.809 Hom.: 8104

Bravo AF: 0.811

Asia WGS AF: 0.703 AC: 2445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.39
PhyloP100		-0.19
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: rs2117114; hg19: chr1-226571619;