rs3219123

Variant names:

• chr1-226367647-G-A
• rs3219123
• NM_001618.4:c.2278-39C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-226367647-G-A
• chr1-226367647-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.2278-39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0511 in 1,611,774 control chromosomes in the GnomAD database, including 2,511 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 0.040 (197 hom., cov: 32)
  • Exomes 𝑓: 0.052 (2314 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489
• Publications: 17 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.058 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP1	NM_001618.4	c.2278-39C>T		intron_variant	Intron 16 of 22	ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10	c.2278-39C>T		intron_variant	Intron 16 of 22	1	NM_001618.4	ENSP00000355759.5

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6129 AN: 152156 Hom.: 198 Cov.: 32

Gnomad AFR AF: 0.00965

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0407

Gnomad ASJ AF: 0.0850

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0462

Gnomad FIN AF: 0.0375

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0595

Gnomad OTH AF: 0.0498

GnomAD2 exomes AF: 0.0445 AC: 11130 AN: 250192 AF XY: 0.0466

Gnomad AFR exome AF: 0.00862

Gnomad AMR exome AF: 0.0237

Gnomad ASJ exome AF: 0.0900

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.0354

Gnomad NFE exome AF: 0.0601

Gnomad OTH exome AF: 0.0512

GnomAD4 exome AF: 0.0522 AC: 76245 AN: 1459500 Hom.: 2314 Cov.: 32 AF XY: 0.0529 AC XY: 38394 AN XY: 726196

African (AFR) AF: 0.00720 AC: 241 AN: 33476

American (AMR) AF: 0.0259 AC: 1158 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0901 AC: 2354 AN: 26124

East Asian (EAS) AF: 0.000403 AC: 16 AN: 39690

South Asian (SAS) AF: 0.0469 AC: 4047 AN: 86226

European-Finnish (FIN) AF: 0.0357 AC: 1856 AN: 52016

Middle Eastern (MID) AF: 0.0982 AC: 566 AN: 5766

European-Non Finnish (NFE) AF: 0.0564 AC: 62644 AN: 1111136

Other (OTH) AF: 0.0557 AC: 3363 AN: 60350

GnomAD4 genome AF: 0.0402 AC: 6128 AN: 152274 Hom.: 197 Cov.: 32 AF XY: 0.0390 AC XY: 2903 AN XY: 74472

African (AFR) AF: 0.00963 AC: 400 AN: 41558

American (AMR) AF: 0.0406 AC: 621 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0850 AC: 295 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0467 AC: 225 AN: 4822

European-Finnish (FIN) AF: 0.0375 AC: 398 AN: 10616

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0595 AC: 4049 AN: 68030

Other (OTH) AF: 0.0492 AC: 104 AN: 2112

Alfa AF: 0.0462 Hom.: 143

Bravo AF: 0.0385

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.50
PhyloP100		0.49
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: rs3219123; hg19: chr1-226555348; COSMIC: COSV107470859; COSMIC: COSV107470859;