NM_001618.4:c.243C>T

Variant names:

• chr1-226402257-G-A
• rs1805404
• NM_001618.4:c.243C>T

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.243C>T​(p.Asp81Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,614,006 control chromosomes in the GnomAD database, including 27,930 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 0.18 (2956 hom., cov: 33)
  • Exomes 𝑓: 0.17 (24974 hom.)
• Consequence: PARP1 NM_001618.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.16
• Publications: 37 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

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=3.16 with no splicing effect.
• 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 rank	MANE	Protein	UniProt
PARP1	NM_001618.4	c.243C>T	p.Asp81Asp	synonymous_variant	Exon 2 of 23	ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10	c.243C>T	p.Asp81Asp	synonymous_variant	Exon 2 of 23	1	NM_001618.4	ENSP00000355759.5

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27223 AN: 152084 Hom.: 2944 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.177

GnomAD2 exomes AF: 0.218 AC: 54895 AN: 251372 AF XY: 0.204

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.426

Gnomad ASJ exome AF: 0.159

Gnomad EAS exome AF: 0.448

Gnomad FIN exome AF: 0.234

Gnomad NFE exome AF: 0.166

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.171 AC: 250468 AN: 1461804 Hom.: 24974 Cov.: 34 AF XY: 0.168 AC XY: 122451 AN XY: 727214

African (AFR) AF: 0.128 AC: 4289 AN: 33480

American (AMR) AF: 0.405 AC: 18111 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 4083 AN: 26136

East Asian (EAS) AF: 0.421 AC: 16694 AN: 39700

South Asian (SAS) AF: 0.107 AC: 9228 AN: 86258

European-Finnish (FIN) AF: 0.233 AC: 12443 AN: 53342

Middle Eastern (MID) AF: 0.153 AC: 883 AN: 5766

European-Non Finnish (NFE) AF: 0.157 AC: 174150 AN: 1112006

Other (OTH) AF: 0.175 AC: 10587 AN: 60394

GnomAD4 genome AF: 0.179 AC: 27278 AN: 152202 Hom.: 2956 Cov.: 33 AF XY: 0.184 AC XY: 13676 AN XY: 74412

African (AFR) AF: 0.131 AC: 5441 AN: 41532

American (AMR) AF: 0.310 AC: 4739 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3468

East Asian (EAS) AF: 0.429 AC: 2215 AN: 5162

South Asian (SAS) AF: 0.113 AC: 546 AN: 4830

European-Finnish (FIN) AF: 0.233 AC: 2472 AN: 10596

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10836 AN: 68002

Other (OTH) AF: 0.178 AC: 376 AN: 2116

Alfa AF: 0.146 Hom.: 1047

Bravo AF: 0.186

Asia WGS AF: 0.242 AC: 842 AN: 3478

EpiCase AF: 0.149

EpiControl AF: 0.155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	10
DANN	Benign	0.49
PhyloP100		3.2
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.8
Mutation Taster		=94/6	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: rs1805404; hg19: chr1-226589958; COSMIC: COSV64687027;