1-226383139-T-C

Variant names:

• chr1-226383139-T-C
• rs1805415
• NM_001618.4:c.1056A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001618.4(PARP1):​c.1056A>G​(p.Lys352Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 1,612,388 control chromosomes in the GnomAD database, including 558,644 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 0.83 (52689 hom., cov: 34)
  • Exomes 𝑓: 0.83 (505955 hom.)
• Consequence: PARP1 NM_001618.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101
• Publications: 39 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-0.101 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP1	NM_001618.4	c.1056A>G	p.Lys352Lys	synonymous_variant	Exon 8 of 23	ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10	c.1056A>G	p.Lys352Lys	synonymous_variant	Exon 8 of 23	1	NM_001618.4	ENSP00000355759.5

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125924 AN: 152150 Hom.: 52662 Cov.: 34

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.827

GnomAD2 exomes AF: 0.783 AC: 196977 AN: 251452 AF XY: 0.797

Gnomad AFR exome AF: 0.900

Gnomad AMR exome AF: 0.575

Gnomad ASJ exome AF: 0.840

Gnomad EAS exome AF: 0.553

Gnomad FIN exome AF: 0.766

Gnomad NFE exome AF: 0.834

Gnomad OTH exome AF: 0.807

GnomAD4 exome AF: 0.830 AC: 1211228 AN: 1460120 Hom.: 505955 Cov.: 39 AF XY: 0.832 AC XY: 604714 AN XY: 726440

African (AFR) AF: 0.898 AC: 30027 AN: 33432

American (AMR) AF: 0.596 AC: 26647 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 22040 AN: 26132

East Asian (EAS) AF: 0.580 AC: 23026 AN: 39686

South Asian (SAS) AF: 0.893 AC: 77008 AN: 86206

European-Finnish (FIN) AF: 0.767 AC: 40946 AN: 53416

Middle Eastern (MID) AF: 0.849 AC: 4463 AN: 5258

European-Non Finnish (NFE) AF: 0.844 AC: 937190 AN: 1110984

Other (OTH) AF: 0.827 AC: 49881 AN: 60290

GnomAD4 genome AF: 0.827 AC: 126001 AN: 152268 Hom.: 52689 Cov.: 34 AF XY: 0.823 AC XY: 61254 AN XY: 74454

African (AFR) AF: 0.892 AC: 37094 AN: 41570

American (AMR) AF: 0.692 AC: 10594 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2919 AN: 3470

East Asian (EAS) AF: 0.571 AC: 2946 AN: 5158

South Asian (SAS) AF: 0.888 AC: 4282 AN: 4822

European-Finnish (FIN) AF: 0.767 AC: 8131 AN: 10604

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

European-Non Finnish (NFE) AF: 0.841 AC: 57189 AN: 68020

Other (OTH) AF: 0.826 AC: 1747 AN: 2116

Alfa AF: 0.842 Hom.: 47428

Bravo AF: 0.822

Asia WGS AF: 0.765 AC: 2661 AN: 3478

EpiCase AF: 0.851

EpiControl AF: 0.845

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.7
DANN	Benign	0.45
PhyloP100		-0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs1805415; hg19: chr1-226570840; COSMIC: COSV64689254;