1-226367250-T-C

Variant names:

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

Variant summary

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

The ENST00000366794.10(PARP1):​c.2406+230A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.059 in 568,548 control chromosomes in the GnomAD database, including 1,187 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 0.051 (237 hom., cov: 32)
  • Exomes 𝑓: 0.062 (950 hom.)
• Consequence: PARP1 ENST00000366794.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0704 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000366794.10. 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>G		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>G		intron	N/A	ENSP00000355759.5
	PARP1	ENST00000490921.5	TSL:2	n.1164A>G		non_coding_transcript_exon	Exon 3 of 8
	PARP1	ENST00000676685.1		n.2861A>G		non_coding_transcript_exon	Exon 17 of 21

Frequencies

GnomAD3 genomes AF: 0.0509 AC: 7748 AN: 152166 Hom.: 237 Cov.: 32

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0596

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0768

Gnomad FIN AF: 0.0392

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0702

Gnomad OTH AF: 0.0804

GnomAD4 exome AF: 0.0620 AC: 25805 AN: 416264 Hom.: 950 Cov.: 4 AF XY: 0.0629 AC XY: 13848 AN XY: 220124

African (AFR) AF: 0.0211 AC: 250 AN: 11876

American (AMR) AF: 0.0554 AC: 1043 AN: 18842

Ashkenazi Jewish (ASJ) AF: 0.0456 AC: 590 AN: 12932

East Asian (EAS) AF: 0.00112 AC: 31 AN: 27612

South Asian (SAS) AF: 0.0727 AC: 3277 AN: 45098

European-Finnish (FIN) AF: 0.0408 AC: 1041 AN: 25520

Middle Eastern (MID) AF: 0.0829 AC: 146 AN: 1762

European-Non Finnish (NFE) AF: 0.0719 AC: 17880 AN: 248570

Other (OTH) AF: 0.0643 AC: 1547 AN: 24052

GnomAD4 genome AF: 0.0509 AC: 7744 AN: 152284 Hom.: 237 Cov.: 32 AF XY: 0.0502 AC XY: 3740 AN XY: 74462

African (AFR) AF: 0.0203 AC: 845 AN: 41564

American (AMR) AF: 0.0595 AC: 911 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 146 AN: 3470

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5188

South Asian (SAS) AF: 0.0769 AC: 371 AN: 4826

European-Finnish (FIN) AF: 0.0392 AC: 416 AN: 10614

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0702 AC: 4773 AN: 68002

Other (OTH) AF: 0.0791 AC: 167 AN: 2112

Alfa AF: 0.0523 Hom.: 142

Bravo AF: 0.0520

Asia WGS AF: 0.0530 AC: 184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.1
DANN	Benign	0.73
PhyloP100		-0.38
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: rs3219125; hg19: chr1-226554951; COSMIC: COSV64689699; COSMIC: COSV64689699;