rs1136410

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001618.4(PARP1):ā€‹c.2285T>Cā€‹(p.Val762Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,613,852 control chromosomes in the GnomAD database, including 27,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.16 ( 2595 hom., cov: 32)
Exomes š‘“: 0.17 ( 24640 hom. )

Consequence

PARP1
NM_001618.4 missense

Scores

1
7
10

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 8.94
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0029218793).
BP6
Variant 1-226367601-A-G is Benign according to our data. Variant chr1-226367601-A-G is described in ClinVar as [Benign]. Clinvar id is 1261945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PARP1NM_001618.4 linkuse as main transcriptc.2285T>C p.Val762Ala missense_variant 17/23 ENST00000366794.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PARP1ENST00000366794.10 linkuse as main transcriptc.2285T>C p.Val762Ala missense_variant 17/231 NM_001618.4 P1

Frequencies

GnomAD3 genomes
AF:
0.157
AC:
23915
AN:
152050
Hom.:
2589
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0539
Gnomad AMI
AF:
0.0724
Gnomad AMR
AF:
0.302
Gnomad ASJ
AF:
0.158
Gnomad EAS
AF:
0.429
Gnomad SAS
AF:
0.112
Gnomad FIN
AF:
0.234
Gnomad MID
AF:
0.136
Gnomad NFE
AF:
0.159
Gnomad OTH
AF:
0.164
GnomAD3 exomes
AF:
0.213
AC:
53567
AN:
251412
Hom.:
7750
AF XY:
0.200
AC XY:
27205
AN XY:
135878
show subpopulations
Gnomad AFR exome
AF:
0.0487
Gnomad AMR exome
AF:
0.423
Gnomad ASJ exome
AF:
0.160
Gnomad EAS exome
AF:
0.448
Gnomad SAS exome
AF:
0.103
Gnomad FIN exome
AF:
0.234
Gnomad NFE exome
AF:
0.166
Gnomad OTH exome
AF:
0.192
GnomAD4 exome
AF:
0.169
AC:
247339
AN:
1461684
Hom.:
24640
Cov.:
33
AF XY:
0.167
AC XY:
121143
AN XY:
727168
show subpopulations
Gnomad4 AFR exome
AF:
0.0486
Gnomad4 AMR exome
AF:
0.402
Gnomad4 ASJ exome
AF:
0.156
Gnomad4 EAS exome
AF:
0.420
Gnomad4 SAS exome
AF:
0.107
Gnomad4 FIN exome
AF:
0.233
Gnomad4 NFE exome
AF:
0.157
Gnomad4 OTH exome
AF:
0.169
GnomAD4 genome
AF:
0.157
AC:
23938
AN:
152168
Hom.:
2595
Cov.:
32
AF XY:
0.163
AC XY:
12120
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.0539
Gnomad4 AMR
AF:
0.303
Gnomad4 ASJ
AF:
0.158
Gnomad4 EAS
AF:
0.429
Gnomad4 SAS
AF:
0.112
Gnomad4 FIN
AF:
0.234
Gnomad4 NFE
AF:
0.159
Gnomad4 OTH
AF:
0.166
Alfa
AF:
0.165
Hom.:
6011
Bravo
AF:
0.162
TwinsUK
AF:
0.147
AC:
544
ALSPAC
AF:
0.159
AC:
612
ESP6500AA
AF:
0.0529
AC:
233
ESP6500EA
AF:
0.159
AC:
1371
ExAC
AF:
0.202
AC:
24493
Asia WGS
AF:
0.229
AC:
798
AN:
3478
EpiCase
AF:
0.149
EpiControl
AF:
0.155

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxOct 08, 2019This variant is associated with the following publications: (PMID: 24392019, 29484706, 23633189, 15342424, 23040216, 24853559, 24489833, 22624032, 23608917, 23073772, 18716896, 23910651, 19484672, 18054108, 21037106, 20196871, 17214964) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.41
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.38
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.10
T
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.87
D
MetaRNN
Benign
0.0029
T
MetaSVM
Benign
-0.84
T
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
5.5e-11
P
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.18
Sift
Benign
0.18
T
Sift4G
Benign
0.51
T
Polyphen
0.73
P
Vest4
0.31
MPC
0.84
ClinPred
0.055
T
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8
Varity_R
0.58
gMVP
0.50

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: rs1136410; hg19: chr1-226555302; COSMIC: COSV64689246; COSMIC: COSV64689246; API