Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_178013.4(PRIMA1):c.420G>A(p.Ser140Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 1,612,388 control chromosomes in the GnomAD database, including 323,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 26673 hom., cov: 31)

Exomes 𝑓: 0.63 ( 296338 hom. )

Consequence

PRIMA1
NM_178013.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.83

Publications

19 publications found

Variant links:

Genes affected

PRIMA1 (HGNC:18319): (proline rich membrane anchor 1) The product of this gene functions to organize acetylcholinesterase (AChE) into tetramers, and to anchor AChE at neural cell membranes. [provided by RefSeq, Nov 2008]

PRIMA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 14-93721486-C-T is Benign according to our data. Variant chr14-93721486-C-T is described in ClinVar as Benign. ClinVar VariationId is 586377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.83 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178013.4. 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
	PRIMA1	NM_178013.4	MANE Select	c.420G>A	p.Ser140Ser	synonymous	Exon 5 of 5	NP_821092.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PRIMA1	ENST00000393140.6	TSL:1 MANE Select	c.420G>A	p.Ser140Ser	synonymous	Exon 5 of 5	ENSP00000376848.1
PRIMA1	ENST00000393143.5	TSL:1	c.420G>A	p.Ser140Ser	synonymous	Exon 4 of 4	ENSP00000376851.1
PRIMA1	ENST00000477603.5	TSL:1	n.*216G>A		non_coding_transcript_exon	Exon 6 of 6	ENSP00000434370.1

Frequencies

GnomAD3 genomes

AF:

0.582

AC:

88386

AN:

151830

Hom.:

26667

Cov.:

show subpopulations

Gnomad AFR

AF:

0.428

Gnomad AMI

AF:

0.620

Gnomad AMR

AF:

0.671

Gnomad ASJ

AF:

0.725

Gnomad EAS

AF:

0.341

Gnomad SAS

AF:

0.546

Gnomad FIN

AF:

0.636

Gnomad MID

AF:

0.671

Gnomad NFE

AF:

0.659

Gnomad OTH

AF:

0.610

GnomAD2 exomes

AF:

0.607

AC:

152360

AN:

251012

AF XY:

0.610

show subpopulations

Gnomad AFR exome

AF:

0.419

Gnomad AMR exome

AF:

0.668

Gnomad ASJ exome

AF:

0.728

Gnomad EAS exome

AF:

0.328

Gnomad FIN exome

AF:

0.632

Gnomad NFE exome

AF:

0.658

Gnomad OTH exome

AF:

0.630

GnomAD4 exome

AF:

0.633

AC:

924802

AN:

1460440

Hom.:

296338

Cov.:

AF XY:

0.632

AC XY:

459312

AN XY:

726606

show subpopulations

African (AFR)

AF:

0.419

AC:

14006

AN:

33448

American (AMR)

AF:

0.667

AC:

29810

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.725

AC:

18933

AN:

26122

East Asian (EAS)

AF:

0.349

AC:

13839

AN:

39696

South Asian (SAS)

AF:

0.550

AC:

47446

AN:

86208

European-Finnish (FIN)

AF:

0.629

AC:

33533

AN:

53310

Middle Eastern (MID)

AF:

0.669

AC:

3850

AN:

5758

European-Non Finnish (NFE)

AF:

0.654

AC:

726090

AN:

1110868

Other (OTH)

AF:

0.618

AC:

37295

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

15631

31263

46894

62526

78157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18852

37704

56556

75408

94260

<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:

0.582

AC:

88431

AN:

151948

Hom.:

26673

Cov.:

AF XY:

0.583

AC XY:

43262

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.428

AC:

17757

AN:

41450

American (AMR)

AF:

0.671

AC:

10256

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.725

AC:

2514

AN:

3468

East Asian (EAS)

AF:

0.342

AC:

1765

AN:

5156

South Asian (SAS)

AF:

0.547

AC:

2616

AN:

4780

European-Finnish (FIN)

AF:

0.636

AC:

6710

AN:

10558

Middle Eastern (MID)

AF:

0.670

AC:

197

AN:

294

European-Non Finnish (NFE)

AF:

0.659

AC:

44779

AN:

67934

Other (OTH)

AF:

0.603

AC:

1273

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1852

3705

5557

7410

9262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

740

1480

2220

2960

3700

<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:

0.632

Hom.:

88953

Bravo

AF:

0.577

Asia WGS

AF:

0.445

AC:

1555

AN:

3478

EpiCase

AF:

0.666

EpiControl

AF:

0.666

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Familial sleep-related hypermotor epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.13

(source)

DANN

Benign

0.61

PhyloP100

-1.8

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over