1-226363223-G-C

Variant names:

• chr1-226363223-G-C
• rs747657
• NM_001618.4:c.2787-63C>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.2787-63C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 1,072,544 control chromosomes in the GnomAD database, including 214,043 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 0.58 (26425 hom., cov: 32)
  • Exomes 𝑓: 0.63 (187618 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.616
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 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.2787-63C>G		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.2787-63C>G		intron	N/A	ENSP00000355759.5
	PARP1	ENST00000498787.2	TSL:2	n.4596C>G		non_coding_transcript_exon	Exon 5 of 7
	PARP1	ENST00000676685.1		n.5158C>G		non_coding_transcript_exon	Exon 19 of 21

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87768 AN: 151954 Hom.: 26426 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.606

GnomAD4 exome AF: 0.629 AC: 578578 AN: 920472 Hom.: 187618 AF XY: 0.632 AC XY: 304304 AN XY: 481414

African (AFR) AF: 0.441 AC: 10181 AN: 23094

American (AMR) AF: 0.463 AC: 20378 AN: 43984

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 15719 AN: 22792

East Asian (EAS) AF: 0.207 AC: 7727 AN: 37300

South Asian (SAS) AF: 0.637 AC: 47905 AN: 75212

European-Finnish (FIN) AF: 0.598 AC: 31667 AN: 52976

Middle Eastern (MID) AF: 0.669 AC: 3118 AN: 4658

European-Non Finnish (NFE) AF: 0.672 AC: 415488 AN: 617854

Other (OTH) AF: 0.620 AC: 26395 AN: 42602

GnomAD4 genome AF: 0.577 AC: 87799 AN: 152072 Hom.: 26425 Cov.: 32 AF XY: 0.573 AC XY: 42630 AN XY: 74338

African (AFR) AF: 0.456 AC: 18920 AN: 41476

American (AMR) AF: 0.543 AC: 8302 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2402 AN: 3466

East Asian (EAS) AF: 0.194 AC: 1003 AN: 5170

South Asian (SAS) AF: 0.626 AC: 3020 AN: 4822

European-Finnish (FIN) AF: 0.601 AC: 6346 AN: 10556

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45615 AN: 67994

Other (OTH) AF: 0.606 AC: 1276 AN: 2106

Alfa AF: 0.625 Hom.: 3770

Bravo AF: 0.563

Asia WGS AF: 0.459 AC: 1597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.47
DANN	Benign	0.66
PhyloP100		-0.62
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: rs747657; hg19: chr1-226550924; COSMIC: COSV64690496; COSMIC: COSV64690496;