rs3219142

Variant names:

• chr1-226364367-G-A
• rs3219142
• NM_001618.4:c.2659-297C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-226364367-G-A
• chr1-226364367-G-C
• chr1-226364367-G-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.2659-297C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 386,900 control chromosomes in the GnomAD database, including 5,762 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 0.14 (2032 hom., cov: 32)
  • Exomes 𝑓: 0.16 (3730 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 14 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.196 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.2659-297C>T		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.2659-297C>T		intron	N/A	ENSP00000355759.5	P09874
	PARP1	ENST00000922077.1		c.2653-297C>T		intron	N/A	ENSP00000592136.1
	PARP1	ENST00000922078.1		c.2653-297C>T		intron	N/A	ENSP00000592137.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21708 AN: 152030 Hom.: 2030 Cov.: 32

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0329

Gnomad SAS AF: 0.0857

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.135

GnomAD4 exome AF: 0.165 AC: 38698 AN: 234752 Hom.: 3730 Cov.: 0 AF XY: 0.157 AC XY: 19749 AN XY: 126190

African (AFR) AF: 0.0359 AC: 239 AN: 6652

American (AMR) AF: 0.196 AC: 2425 AN: 12350

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 1481 AN: 6230

East Asian (EAS) AF: 0.0346 AC: 391 AN: 11292

South Asian (SAS) AF: 0.0933 AC: 3918 AN: 42002

European-Finnish (FIN) AF: 0.204 AC: 2140 AN: 10496

Middle Eastern (MID) AF: 0.129 AC: 109 AN: 844

European-Non Finnish (NFE) AF: 0.196 AC: 26018 AN: 132732

Other (OTH) AF: 0.163 AC: 1977 AN: 12154

GnomAD4 genome AF: 0.143 AC: 21704 AN: 152148 Hom.: 2032 Cov.: 32 AF XY: 0.143 AC XY: 10626 AN XY: 74376

African (AFR) AF: 0.0374 AC: 1553 AN: 41528

American (AMR) AF: 0.173 AC: 2639 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 806 AN: 3466

East Asian (EAS) AF: 0.0330 AC: 171 AN: 5184

South Asian (SAS) AF: 0.0853 AC: 411 AN: 4816

European-Finnish (FIN) AF: 0.204 AC: 2154 AN: 10554

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13491 AN: 67988

Other (OTH) AF: 0.134 AC: 283 AN: 2112

Alfa AF: 0.173 Hom.: 4695

Bravo AF: 0.135

Asia WGS AF: 0.0610 AC: 210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
DANN	Benign	0.68
PhyloP100		0.061
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: rs3219142; hg19: chr1-226552068;