dbSNP rs7218283: PIMREG:c.*15-3A>C (chr17-6450359-A-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_019013.3(PIMREG):c.*15-3A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 1,556,426 control chromosomes in the GnomAD database, including 613,023 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.90 ( 61851 hom., cov: 31)

Exomes 𝑓: 0.89 ( 551172 hom. )

Consequence

PIMREG
NM_019013.3 splice_region, intron

Scores

Splicing: ADA: 0.0001555

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.170

Publications

16 publications found

Variant links:

Genes affected

PIMREG (HGNC:25483): (PICALM interacting mitotic regulator) Predicted to be involved in cell division. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PIMREG links:

LOC107985017 (HGNC:):

LOC107985017 links:

Genome browser will be placed here

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=-0.77).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIMREG	NM_019013.3 link	c.*15-3A>C		splice_region_variant, intron_variant	Intron 5 of 5	ENST00000572447.6	NP_061886.2	Q9BSJ6-2A0A0S2Z5C7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIMREG	ENST00000572447.6 link	c.*15-3A>C		splice_region_variant, intron_variant	Intron 5 of 5	1	NM_019013.3	ENSP00000459235.1		Q9BSJ6-2

Frequencies

GnomAD3 genomes

AF:

0.901

AC:

136905

AN:

152024

Hom.:

61804

Cov.:

show subpopulations

Gnomad AFR

AF:

0.950

Gnomad AMI

AF:

0.897

Gnomad AMR

AF:

0.883

Gnomad ASJ

AF:

0.879

Gnomad EAS

AF:

0.855

Gnomad SAS

AF:

0.866

Gnomad FIN

AF:

0.863

Gnomad MID

AF:

0.911

Gnomad NFE

AF:

0.887

Gnomad OTH

AF:

0.899

GnomAD2 exomes

AF:

0.877

AC:

151189

AN:

172434

AF XY:

0.876

show subpopulations

Gnomad AFR exome

AF:

0.950

Gnomad AMR exome

AF:

0.861

Gnomad ASJ exome

AF:

0.880

Gnomad EAS exome

AF:

0.847

Gnomad FIN exome

AF:

0.863

Gnomad NFE exome

AF:

0.885

Gnomad OTH exome

AF:

0.877

GnomAD4 exome

AF:

0.886

AC:

1243593

AN:

1404284

Hom.:

551172

Cov.:

AF XY:

0.885

AC XY:

615224

AN XY:

695048

show subpopulations

African (AFR)

AF:

0.951

AC:

30960

AN:

32566

American (AMR)

AF:

0.861

AC:

32725

AN:

38016

Ashkenazi Jewish (ASJ)

AF:

0.882

AC:

22412

AN:

25408

East Asian (EAS)

AF:

0.879

AC:

33107

AN:

37682

South Asian (SAS)

AF:

0.861

AC:

69493

AN:

80756

European-Finnish (FIN)

AF:

0.862

AC:

30591

AN:

35478

Middle Eastern (MID)

AF:

0.909

AC:

5193

AN:

5714

European-Non Finnish (NFE)

AF:

0.887

AC:

967112

AN:

1089774

Other (OTH)

AF:

0.883

AC:

52000

AN:

58890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

6597

13195

19792

26390

32987

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21136

42272

63408

84544

105680

<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:

0.901

AC:

137009

AN:

152142

Hom.:

61851

Cov.:

AF XY:

0.900

AC XY:

66950

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.950

AC:

39448

AN:

41524

American (AMR)

AF:

0.883

AC:

13521

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.879

AC:

3051

AN:

3472

East Asian (EAS)

AF:

0.854

AC:

4403

AN:

5154

South Asian (SAS)

AF:

0.865

AC:

4160

AN:

4812

European-Finnish (FIN)

AF:

0.863

AC:

9128

AN:

10576

Middle Eastern (MID)

AF:

0.915

AC:

269

AN:

294

European-Non Finnish (NFE)

AF:

0.887

AC:

60317

AN:

67984

Other (OTH)

AF:

0.898

AC:

1894

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

687

1373

2060

2746

3433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

904

1808

2712

3616

4520

<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:

0.889

Hom.:

68396

Bravo

AF:

0.903

Asia WGS

AF:

0.857

AC:

2979

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.5

(source)

DANN

Benign

0.78

PhyloP100

0.17

Mutation Taster

=45/55

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.096

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over