rs3219149

Variant names:

• chr1-226360716-C-A
• rs3219149
• NM_001618.4:c.*744G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-226360716-C-A
• chr1-226360716-C-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.*744G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 223,584 control chromosomes in the GnomAD database, including 121 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 0.011 (96 hom., cov: 31)
  • Exomes 𝑓: 0.010 (25 hom.)
• Consequence: PARP1 NM_001618.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• Publications: 3 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=-0.49).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP1	NM_001618.4	c.*744G>T		3_prime_UTR_variant	Exon 23 of 23	ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10	c.*744G>T		3_prime_UTR_variant	Exon 23 of 23	1	NM_001618.4	ENSP00000355759.5

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1715 AN: 152102 Hom.: 94 Cov.: 31

Gnomad AFR AF: 0.00203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0891

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0328

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000661

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0173

GnomAD4 exome AF: 0.0103 AC: 735 AN: 71364 Hom.: 25 Cov.: 0 AF XY: 0.00959 AC XY: 316 AN XY: 32938

African (AFR) AF: 0.00210 AC: 7 AN: 3336

American (AMR) AF: 0.105 AC: 224 AN: 2138

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4552

East Asian (EAS) AF: 0.0424 AC: 434 AN: 10232

South Asian (SAS) AF: 0.00162 AC: 1 AN: 618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 438

European-Non Finnish (NFE) AF: 0.000522 AC: 23 AN: 44030

Other (OTH) AF: 0.00770 AC: 46 AN: 5974

GnomAD4 genome AF: 0.0113 AC: 1721 AN: 152220 Hom.: 96 Cov.: 31 AF XY: 0.0129 AC XY: 957 AN XY: 74434

African (AFR) AF: 0.00202 AC: 84 AN: 41534

American (AMR) AF: 0.0894 AC: 1367 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0329 AC: 170 AN: 5172

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4826

European-Finnish (FIN) AF: 0.000661 AC: 7 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000691 AC: 47 AN: 68022

Other (OTH) AF: 0.0171 AC: 36 AN: 2108

Alfa AF: 0.00283 Hom.: 0

Bravo AF: 0.0207

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.060
DANN	Benign	0.80
PhyloP100		-2.1
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: rs3219149; hg19: chr1-226548417;