chr1-226377135-G-A

Variant names:

• chr1-226377135-G-A
• rs13306137
• NM_001618.4:c.1914C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_001618.4(PARP1):​c.1914C>T​(p.Phe638Phe) variant causes a synonymous change. The variant allele was found at a frequency of 0.00145 in 1,614,016 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (44 hom.)
• Consequence: PARP1 NM_001618.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 5.29
• Publications: 4 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=-0.28).
• BP6: Variant 1-226377135-G-A is Benign according to our data. Variant chr1-226377135-G-A is described in ClinVar as Benign. ClinVar VariationId is 711740.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00143 (218/152298) while in subpopulation EAS AF = 0.029 (150/5180). AF 95% confidence interval is 0.0252. There are 3 homozygotes in GnomAd4. There are 125 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.1914C>T	p.Phe638Phe	synonymous	Exon 13 of 23	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.1914C>T	p.Phe638Phe	synonymous	Exon 13 of 23	ENSP00000355759.5	P09874
	PARP1	ENST00000922077.1		c.1908C>T	p.Phe636Phe	synonymous	Exon 13 of 23	ENSP00000592136.1
	PARP1	ENST00000922078.1		c.1908C>T	p.Phe636Phe	synonymous	Exon 13 of 23	ENSP00000592137.1

Frequencies

GnomAD3 genomes AF: 0.00144 AC: 219 AN: 152180 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.0289

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00210 AC: 528 AN: 251480 AF XY: 0.00207

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00883

Gnomad EAS exome AF: 0.0207

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000193

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00145 AC: 2121 AN: 1461718 Hom.: 44 Cov.: 32 AF XY: 0.00144 AC XY: 1045 AN XY: 727164

African (AFR) AF: 0.0000597 AC: 2 AN: 33474

American (AMR) AF: 0.000134 AC: 6 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00834 AC: 218 AN: 26136

East Asian (EAS) AF: 0.0395 AC: 1568 AN: 39698

South Asian (SAS) AF: 0.000997 AC: 86 AN: 86246

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

Middle Eastern (MID) AF: 0.000707 AC: 4 AN: 5658

European-Non Finnish (NFE) AF: 0.0000989 AC: 110 AN: 1111988

Other (OTH) AF: 0.00207 AC: 125 AN: 60376

GnomAD4 genome AF: 0.00143 AC: 218 AN: 152298 Hom.: 3 Cov.: 32 AF XY: 0.00168 AC XY: 125 AN XY: 74480

African (AFR) AF: 0.000192 AC: 8 AN: 41562

American (AMR) AF: 0.0000654 AC: 1 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3470

East Asian (EAS) AF: 0.0290 AC: 150 AN: 5180

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68026

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000807 Hom.: 0

Bravo AF: 0.00138

Asia WGS AF: 0.00895 AC: 31 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	PARP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	13
DANN	Benign	0.72
PhyloP100		5.3
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs13306137; hg19: chr1-226564836;