rs3754376

Variant names:

• chr1-226373363-C-A
• rs3754376
• NM_001618.4:c.2070+863G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-226373363-C-A
• chr1-226373363-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.2070+863G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,074 control chromosomes in the GnomAD database, including 25,006 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 0.56 (25006 hom., cov: 32)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.366
• Publications: 11 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 = 0.665 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.2070+863G>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.2070+863G>T		intron	N/A	ENSP00000355759.5
	PARP1	ENST00000677203.1		c.1942-2846G>T		intron	N/A	ENSP00000503396.1
	PARP1	ENST00000676565.1		n.1842+863G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84458 AN: 151956 Hom.: 25011 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.592

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.556 AC: 84482 AN: 152074 Hom.: 25006 Cov.: 32 AF XY: 0.552 AC XY: 41048 AN XY: 74332

African (AFR) AF: 0.380 AC: 15778 AN: 41476

American (AMR) AF: 0.537 AC: 8205 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2396 AN: 3470

East Asian (EAS) AF: 0.194 AC: 1006 AN: 5180

South Asian (SAS) AF: 0.627 AC: 3016 AN: 4814

European-Finnish (FIN) AF: 0.601 AC: 6354 AN: 10570

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.670 AC: 45564 AN: 67964

Other (OTH) AF: 0.593 AC: 1251 AN: 2110

Alfa AF: 0.628 Hom.: 35852

Bravo AF: 0.538

Asia WGS AF: 0.454 AC: 1579 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	3.3
DANN	Benign	0.76
PhyloP100		-0.37
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: rs3754376; hg19: chr1-226561064; COSMIC: COSV64689714; COSMIC: COSV64689714;