rs1805410

Variant names:

• chr1-226380964-T-C
• rs1805410
• NM_001618.4:c.1300+104A>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.1300+104A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,283,754 control chromosomes in the GnomAD database, including 15,711 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 0.13 (1464 hom., cov: 33)
  • Exomes 𝑓: 0.15 (14247 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.197 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.1300+104A>G		intron	N/A	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.1300+104A>G		intron	N/A	ENSP00000355759.5	P09874
	PARP1	ENST00000922077.1		c.1294+104A>G		intron	N/A	ENSP00000592136.1
	PARP1	ENST00000922078.1		c.1294+104A>G		intron	N/A	ENSP00000592137.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20113 AN: 152058 Hom.: 1465 Cov.: 33

Gnomad AFR AF: 0.0962

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0887

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.153 AC: 172733 AN: 1131578 Hom.: 14247 AF XY: 0.155 AC XY: 89259 AN XY: 576800

African (AFR) AF: 0.0968 AC: 2637 AN: 27232

American (AMR) AF: 0.0808 AC: 3507 AN: 43430

Ashkenazi Jewish (ASJ) AF: 0.0964 AC: 2300 AN: 23862

East Asian (EAS) AF: 0.0404 AC: 1539 AN: 38110

South Asian (SAS) AF: 0.196 AC: 15327 AN: 78134

European-Finnish (FIN) AF: 0.156 AC: 8101 AN: 51870

Middle Eastern (MID) AF: 0.152 AC: 609 AN: 3994

European-Non Finnish (NFE) AF: 0.161 AC: 131456 AN: 815752

Other (OTH) AF: 0.148 AC: 7257 AN: 49194

GnomAD4 genome AF: 0.132 AC: 20132 AN: 152176 Hom.: 1464 Cov.: 33 AF XY: 0.133 AC XY: 9894 AN XY: 74392

African (AFR) AF: 0.0962 AC: 3995 AN: 41538

American (AMR) AF: 0.111 AC: 1701 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0887 AC: 308 AN: 3472

East Asian (EAS) AF: 0.0313 AC: 162 AN: 5180

South Asian (SAS) AF: 0.208 AC: 998 AN: 4808

European-Finnish (FIN) AF: 0.164 AC: 1739 AN: 10582

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10591 AN: 67994

Other (OTH) AF: 0.159 AC: 335 AN: 2106

Alfa AF: 0.147 Hom.: 3300

Bravo AF: 0.125

Asia WGS AF: 0.161 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.28
PhyloP100		-0.14
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: rs1805410; hg19: chr1-226568665; COSMIC: COSV64689744;