1-226363477-A-G

Variant names:

• chr1-226363477-A-G
• rs747658
• NM_001618.4:c.2787-317T>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.2787-317T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,032 control chromosomes in the GnomAD database, including 4,240 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 0.22 (4240 hom., cov: 32)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• Publications: 13 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 (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP1	NM_001618.4	c.2787-317T>C		intron_variant	Intron 20 of 22	ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10	c.2787-317T>C		intron_variant	Intron 20 of 22	1	NM_001618.4	ENSP00000355759.5

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33095 AN: 151914 Hom.: 4240 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.218 AC: 33109 AN: 152032 Hom.: 4240 Cov.: 32 AF XY: 0.216 AC XY: 16050 AN XY: 74314

African (AFR) AF: 0.339 AC: 14067 AN: 41444

American (AMR) AF: 0.139 AC: 2125 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3470

East Asian (EAS) AF: 0.337 AC: 1738 AN: 5152

South Asian (SAS) AF: 0.176 AC: 845 AN: 4814

European-Finnish (FIN) AF: 0.166 AC: 1760 AN: 10582

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11494 AN: 67972

Other (OTH) AF: 0.196 AC: 415 AN: 2114

Alfa AF: 0.178 Hom.: 1402

Bravo AF: 0.225

Asia WGS AF: 0.241 AC: 838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.50
DANN	Benign	0.54
PhyloP100		-0.31
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: rs747658; hg19: chr1-226551178;