rs3219125

Variant names:

• chr1-226367250-T-A
• rs3219125
• NM_001618.4:c.2406+230A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-226367250-T-A
• chr1-226367250-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001618.4(PARP1):​c.2406+230A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000024 in 416,484 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

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.2406+230A>T		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.2406+230A>T		intron	N/A	ENSP00000355759.5
	PARP1	ENST00000490921.5	TSL:2	n.1164A>T		non_coding_transcript_exon	Exon 3 of 8
	PARP1	ENST00000676685.1		n.2861A>T		non_coding_transcript_exon	Exon 17 of 21

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000240 AC: 1 AN: 416484 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 220244

African (AFR) AF: 0.00 AC: 0 AN: 11876

American (AMR) AF: 0.00 AC: 0 AN: 18846

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12934

East Asian (EAS) AF: 0.0000362 AC: 1 AN: 27612

South Asian (SAS) AF: 0.00 AC: 0 AN: 45114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 248742

Other (OTH) AF: 0.00 AC: 0 AN: 24056

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.8
DANN	Benign	0.86
PhyloP100		-0.38

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: rs3219125; hg19: chr1-226554951;