rs3754375

Variant names:

• chr1-226373364-A-G
• rs3754375
• NM_001618.4:c.2070+862T>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.2070+862T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,174 control chromosomes in the GnomAD database, including 4,003 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 0.21 (4003 hom., cov: 32)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 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+862T>C		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+862T>C		intron	N/A	ENSP00000355759.5
	PARP1	ENST00000677203.1		c.1942-2847T>C		intron	N/A	ENSP00000503396.1
	PARP1	ENST00000676565.1		n.1842+862T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32407 AN: 152056 Hom.: 4007 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.213 AC: 32409 AN: 152174 Hom.: 4003 Cov.: 32 AF XY: 0.212 AC XY: 15740 AN XY: 74408

African (AFR) AF: 0.323 AC: 13384 AN: 41492

American (AMR) AF: 0.137 AC: 2092 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 483 AN: 3472

East Asian (EAS) AF: 0.339 AC: 1758 AN: 5180

South Asian (SAS) AF: 0.176 AC: 849 AN: 4826

European-Finnish (FIN) AF: 0.166 AC: 1760 AN: 10602

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

European-Non Finnish (NFE) AF: 0.169 AC: 11494 AN: 67992

Other (OTH) AF: 0.192 AC: 405 AN: 2114

Alfa AF: 0.192 Hom.: 400

Bravo AF: 0.219

Asia WGS AF: 0.241 AC: 836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.85
PhyloP100		-0.097
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: rs3754375; hg19: chr1-226561065;