rs2271347

Variant names:

• chr1-226361797-G-A
• rs2271347
• NM_001618.4:c.2963+172C>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.2963+172C>T 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 683,664 control chromosomes in the GnomAD database, including 15,147 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 0.16 (2599 hom., cov: 31)
  • Exomes 𝑓: 0.21 (12548 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635
• Publications: 24 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.234 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP1	NM_001618.4	MANE Select	c.2963+172C>T		intron	N/A	NP_001609.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP1	ENST00000366794.10	TSL:1 MANE Select	c.2963+172C>T		intron	N/A	ENSP00000355759.5
	PARP1	ENST00000468608.1	TSL:3	n.349C>T		non_coding_transcript_exon	Exon 2 of 2
	PARP1	ENST00000677203.1		c.2834+172C>T		intron	N/A	ENSP00000503396.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25033 AN: 151984 Hom.: 2600 Cov.: 31

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.0596

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.206 AC: 109499 AN: 531562 Hom.: 12548 Cov.: 5 AF XY: 0.212 AC XY: 60483 AN XY: 285518

African (AFR) AF: 0.0609 AC: 929 AN: 15244

American (AMR) AF: 0.143 AC: 4667 AN: 32648

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 5116 AN: 17728

East Asian (EAS) AF: 0.0665 AC: 2119 AN: 31886

South Asian (SAS) AF: 0.257 AC: 14529 AN: 56622

European-Finnish (FIN) AF: 0.122 AC: 4699 AN: 38480

Middle Eastern (MID) AF: 0.302 AC: 1100 AN: 3642

European-Non Finnish (NFE) AF: 0.229 AC: 70124 AN: 305770

Other (OTH) AF: 0.210 AC: 6216 AN: 29542

GnomAD4 genome AF: 0.165 AC: 25025 AN: 152102 Hom.: 2599 Cov.: 31 AF XY: 0.160 AC XY: 11860 AN XY: 74350

African (AFR) AF: 0.0607 AC: 2521 AN: 41514

American (AMR) AF: 0.177 AC: 2712 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1030 AN: 3468

East Asian (EAS) AF: 0.0597 AC: 308 AN: 5158

South Asian (SAS) AF: 0.246 AC: 1184 AN: 4822

European-Finnish (FIN) AF: 0.116 AC: 1229 AN: 10586

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15374 AN: 67958

Other (OTH) AF: 0.193 AC: 406 AN: 2106

Alfa AF: 0.213 Hom.: 3726

Bravo AF: 0.163

Asia WGS AF: 0.145 AC: 504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.43
DANN	Benign	0.24
PhyloP100		-0.64
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: rs2271347; hg19: chr1-226549498;