rs3219125

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001618.4(PARP1):​c.2406+230A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.059 in 568,548 control chromosomes in the GnomAD database, including 1,187 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 0.051 ( 237 hom., cov: 32)
Exomes 𝑓: 0.062 ( 950 hom. )

Consequence

PARP1
NM_001618.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.381
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0704 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PARP1NM_001618.4 linkuse as main transcriptc.2406+230A>G intron_variant ENST00000366794.10 NP_001609.2 P09874A0A024R3T8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PARP1ENST00000366794.10 linkuse as main transcriptc.2406+230A>G intron_variant 1 NM_001618.4 ENSP00000355759.5 P09874

Frequencies

GnomAD3 genomes
AF:
0.0509
AC:
7748
AN:
152166
Hom.:
237
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0204
Gnomad AMI
AF:
0.0625
Gnomad AMR
AF:
0.0596
Gnomad ASJ
AF:
0.0421
Gnomad EAS
AF:
0.00346
Gnomad SAS
AF:
0.0768
Gnomad FIN
AF:
0.0392
Gnomad MID
AF:
0.133
Gnomad NFE
AF:
0.0702
Gnomad OTH
AF:
0.0804
GnomAD4 exome
AF:
0.0620
AC:
25805
AN:
416264
Hom.:
950
Cov.:
4
AF XY:
0.0629
AC XY:
13848
AN XY:
220124
show subpopulations
Gnomad4 AFR exome
AF:
0.0211
Gnomad4 AMR exome
AF:
0.0554
Gnomad4 ASJ exome
AF:
0.0456
Gnomad4 EAS exome
AF:
0.00112
Gnomad4 SAS exome
AF:
0.0727
Gnomad4 FIN exome
AF:
0.0408
Gnomad4 NFE exome
AF:
0.0719
Gnomad4 OTH exome
AF:
0.0643
GnomAD4 genome
AF:
0.0509
AC:
7744
AN:
152284
Hom.:
237
Cov.:
32
AF XY:
0.0502
AC XY:
3740
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0203
Gnomad4 AMR
AF:
0.0595
Gnomad4 ASJ
AF:
0.0421
Gnomad4 EAS
AF:
0.00347
Gnomad4 SAS
AF:
0.0769
Gnomad4 FIN
AF:
0.0392
Gnomad4 NFE
AF:
0.0702
Gnomad4 OTH
AF:
0.0791
Alfa
AF:
0.0621
Hom.:
59
Bravo
AF:
0.0520
Asia WGS
AF:
0.0530
AC:
184
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
5.1
DANN
Benign
0.73

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3219125; hg19: chr1-226554951; COSMIC: COSV64689699; COSMIC: COSV64689699; API