rs3219110

Variant names:

• chr1-226370177-T-C
• rs3219110
• NM_001618.4:c.2154+257A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001618.4(PARP1):​c.2154+257A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,812 control chromosomes in the GnomAD database, including 11,927 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 0.39 (11927 hom., cov: 30)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 18 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 = 0.44 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.2154+257A>G		intron	N/A	NP_001609.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP1	ENST00000366794.10	TSL:1 MANE Select	c.2154+257A>G		intron	N/A	ENSP00000355759.5
	PARP1	ENST00000922077.1		c.2148+257A>G		intron	N/A	ENSP00000592136.1
	PARP1	ENST00000922078.1		c.2148+257A>G		intron	N/A	ENSP00000592137.1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 58967 AN: 151694 Hom.: 11926 Cov.: 30

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.389 AC: 58994 AN: 151812 Hom.: 11927 Cov.: 30 AF XY: 0.390 AC XY: 28949 AN XY: 74162

African (AFR) AF: 0.312 AC: 12927 AN: 41408

American (AMR) AF: 0.359 AC: 5477 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1366 AN: 3470

East Asian (EAS) AF: 0.133 AC: 688 AN: 5156

South Asian (SAS) AF: 0.379 AC: 1815 AN: 4786

European-Finnish (FIN) AF: 0.483 AC: 5079 AN: 10520

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30151 AN: 67890

Other (OTH) AF: 0.399 AC: 841 AN: 2108

Alfa AF: 0.434 Hom.: 23901

Bravo AF: 0.373

Asia WGS AF: 0.309 AC: 1075 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	6.1
DANN	Benign	0.57
PhyloP100		1.0
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: rs3219110; hg19: chr1-226557878; COSMIC: COSV64689710;