rs2255403

Variant names:

• chr1-226388569-A-G
• rs2255403
• NM_001618.4:c.717+87T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-226388569-A-G
• chr1-226388569-A-T

Variant summary

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

The NM_001618.4(PARP1):​c.717+87T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 933,016 control chromosomes in the GnomAD database, including 21,663 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 0.19 (3240 hom., cov: 33)
  • Exomes 𝑓: 0.20 (18423 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30
• Publications: 12 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001618.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP1	NM_001618.4	MANE Select	c.717+87T>C		intron	N/A	NP_001609.2	P09874

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP1	ENST00000366794.10	TSL:1 MANE Select	c.717+87T>C		intron	N/A	ENSP00000355759.5	P09874
	PARP1	ENST00000922077.1		c.711+87T>C		intron	N/A	ENSP00000592136.1
	PARP1	ENST00000922078.1		c.711+87T>C		intron	N/A	ENSP00000592137.1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28835 AN: 152128 Hom.: 3228 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.198 AC: 154880 AN: 780770 Hom.: 18423 AF XY: 0.194 AC XY: 80613 AN XY: 415112

African (AFR) AF: 0.155 AC: 3177 AN: 20442

American (AMR) AF: 0.407 AC: 17430 AN: 42816

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 3574 AN: 21668

East Asian (EAS) AF: 0.466 AC: 17000 AN: 36446

South Asian (SAS) AF: 0.184 AC: 13203 AN: 71776

European-Finnish (FIN) AF: 0.234 AC: 12298 AN: 52660

Middle Eastern (MID) AF: 0.164 AC: 729 AN: 4456

European-Non Finnish (NFE) AF: 0.163 AC: 80172 AN: 492670

Other (OTH) AF: 0.193 AC: 7297 AN: 37836

GnomAD4 genome AF: 0.190 AC: 28899 AN: 152246 Hom.: 3240 Cov.: 33 AF XY: 0.196 AC XY: 14572 AN XY: 74430

African (AFR) AF: 0.153 AC: 6370 AN: 41566

American (AMR) AF: 0.311 AC: 4755 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 579 AN: 3468

East Asian (EAS) AF: 0.468 AC: 2422 AN: 5178

South Asian (SAS) AF: 0.197 AC: 951 AN: 4824

European-Finnish (FIN) AF: 0.232 AC: 2463 AN: 10596

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

European-Non Finnish (NFE) AF: 0.160 AC: 10858 AN: 68008

Other (OTH) AF: 0.187 AC: 396 AN: 2114

Alfa AF: 0.170 Hom.: 353

Bravo AF: 0.196

Asia WGS AF: 0.298 AC: 1035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.4
DANN	Benign	0.43
PhyloP100		2.3
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2255403;

hg19: chr1-226576270;

COSMIC: COSV64687805;

COSMIC: COSV64687805;