NM_001618.4:c.-17G>C

Variant names:

• chr1-226407946-C-G
• rs907187
• NM_001618.4:c.-17G>C

Variant summary

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

The NM_001618.4(PARP1):​c.-17G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,610,132 control chromosomes in the GnomAD database, including 28,309 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 0.16 (2730 hom., cov: 32)
  • Exomes 𝑓: 0.17 (25579 hom.)
• Consequence: PARP1 NM_001618.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.951
• Publications: 23 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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 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.-17G>C		5_prime_UTR	Exon 1 of 23	NP_001609.2	P09874

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP1	ENST00000366794.10	TSL:1 MANE Select	c.-17G>C		5_prime_UTR	Exon 1 of 23	ENSP00000355759.5	P09874
	PARP1	ENST00000922077.1		c.-17G>C		5_prime_UTR	Exon 1 of 23	ENSP00000592136.1
	PARP1	ENST00000922078.1		c.-17G>C		5_prime_UTR	Exon 1 of 23	ENSP00000592137.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24523 AN: 151984 Hom.: 2724 Cov.: 32

Gnomad AFR AF: 0.0539

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.169

GnomAD2 exomes AF: 0.214 AC: 52583 AN: 246266 AF XY: 0.201

Gnomad AFR exome AF: 0.0465

Gnomad AMR exome AF: 0.418

Gnomad ASJ exome AF: 0.160

Gnomad EAS exome AF: 0.443

Gnomad FIN exome AF: 0.261

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.173 AC: 252465 AN: 1458040 Hom.: 25579 Cov.: 35 AF XY: 0.170 AC XY: 123645 AN XY: 725378

African (AFR) AF: 0.0483 AC: 1612 AN: 33370

American (AMR) AF: 0.399 AC: 17612 AN: 44186

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 4102 AN: 26008

East Asian (EAS) AF: 0.420 AC: 16547 AN: 39438

South Asian (SAS) AF: 0.107 AC: 9221 AN: 86142

European-Finnish (FIN) AF: 0.263 AC: 13892 AN: 52824

Middle Eastern (MID) AF: 0.150 AC: 863 AN: 5760

European-Non Finnish (NFE) AF: 0.160 AC: 178151 AN: 1110118

Other (OTH) AF: 0.174 AC: 10465 AN: 60194

GnomAD4 genome AF: 0.161 AC: 24545 AN: 152092 Hom.: 2730 Cov.: 32 AF XY: 0.168 AC XY: 12516 AN XY: 74376

African (AFR) AF: 0.0539 AC: 2239 AN: 41550

American (AMR) AF: 0.305 AC: 4659 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 559 AN: 3470

East Asian (EAS) AF: 0.430 AC: 2213 AN: 5146

South Asian (SAS) AF: 0.114 AC: 549 AN: 4824

European-Finnish (FIN) AF: 0.263 AC: 2781 AN: 10566

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.163 AC: 11083 AN: 67928

Other (OTH) AF: 0.170 AC: 358 AN: 2110

Alfa AF: 0.159 Hom.: 387

Bravo AF: 0.164

Asia WGS AF: 0.226 AC: 782 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.70
PhyloP100		0.95
PromoterAI		-0.024	Neutral
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		3.2
Mutation Taster		=300/0	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: rs907187; hg19: chr1-226595647; COSMIC: COSV64687065; COSMIC: COSV64687065;