Genetic Variant NM_022750.4:c.1781-57C>G (chr7-140024942-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022750.4(PARP12):c.1781-57C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0934 in 1,523,382 control chromosomes in the GnomAD database, including 7,333 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 0.076 ( 536 hom., cov: 32)

Exomes 𝑓: 0.095 ( 6797 hom. )

Consequence

PARP12
NM_022750.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0320

Publications

5 publications found

Variant links:

Genes affected

PARP12 (HGNC:21919): (poly(ADP-ribose) polymerase family member 12) Enables protein ADP-ribosylase activity. Involved in protein auto-ADP-ribosylation and protein mono-ADP-ribosylation. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PARP12 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022750.4. 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
	PARP12	NM_022750.4	MANE Select	c.1781-57C>G		intron	N/A	NP_073587.1	Q9H0J9
	PARP12	NR_130117.2		n.1743-57C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PARP12	ENST00000263549.8	TSL:1 MANE Select	c.1781-57C>G	intron	N/A	ENSP00000263549.3	Q9H0J9
PARP12	ENST00000473341.5	TSL:1	n.*376-57C>G	intron	N/A	ENSP00000417730.1	G5E9U9
PARP12	ENST00000851631.1		c.1886-57C>G	intron	N/A	ENSP00000521690.1

Frequencies

GnomAD3 genomes

AF:

0.0759

AC:

11537

AN:

152080

Hom.:

536

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0330

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.0707

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.0508

Gnomad SAS

AF:

0.0259

Gnomad FIN

AF:

0.0450

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.0921

GnomAD4 exome

AF:

0.0954

AC:

130777

AN:

1371184

Hom.:

6797

AF XY:

0.0940

AC XY:

64089

AN XY:

681536

show subpopulations

African (AFR)

AF:

0.0306

AC:

964

AN:

31526

American (AMR)

AF:

0.0552

AC:

2345

AN:

42478

Ashkenazi Jewish (ASJ)

AF:

0.110

AC:

2624

AN:

23906

East Asian (EAS)

AF:

0.0521

AC:

2034

AN:

39012

South Asian (SAS)

AF:

0.0299

AC:

2398

AN:

80198

European-Finnish (FIN)

AF:

0.0535

AC:

2723

AN:

50892

Middle Eastern (MID)

AF:

0.0802

AC:

429

AN:

5352

European-Non Finnish (NFE)

AF:

0.108

AC:

112246

AN:

1040624

Other (OTH)

AF:

0.0877

AC:

5014

AN:

57196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

5088

10176

15263

20351

25439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3830

7660

11490

15320

19150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0758

AC:

11537

AN:

152198

Hom.:

536

Cov.:

AF XY:

0.0725

AC XY:

5398

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0330

AC:

1369

AN:

41522

American (AMR)

AF:

0.0706

AC:

1080

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

378

AN:

3466

East Asian (EAS)

AF:

0.0514

AC:

266

AN:

5180

South Asian (SAS)

AF:

0.0257

AC:

124

AN:

4820

European-Finnish (FIN)

AF:

0.0450

AC:

477

AN:

10610

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.111

AC:

7515

AN:

67996

Other (OTH)

AF:

0.0916

AC:

193

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

538

1077

1615

2154

2692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0417

Hom.:

Bravo

AF:

0.0782

Asia WGS

AF:

0.0370

AC:

128

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.0

(source)

DANN

Benign

0.73

PhyloP100

0.032

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over