rs1057335

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000934.4(SERPINF2):c.1301G>A(p.Arg434Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,614,050 control chromosomes in the GnomAD database, including 34,592 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3125 hom., cov: 33)

Exomes 𝑓: 0.20 ( 31467 hom. )

Consequence

SERPINF2
NM_000934.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0510

Publications

44 publications found

Variant links:

Genes affected

SERPINF2 (HGNC:9075): (serpin family F member 2) This gene encodes a member of the serpin family of serine protease inhibitors. The protein is a major inhibitor of plasmin, which degrades fibrin and various other proteins. Consequently, the proper function of this gene has a major role in regulating the blood clotting pathway. Mutations in this gene result in alpha-2-plasmin inhibitor deficiency, which is characterized by severe hemorrhagic diathesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

SERPINF2 Gene-Disease associations (from GenCC):

alpha-2-plasmin inhibitor deficiency
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

SERPINF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024048686).

BP6

Variant 17-1754359-G-A is Benign according to our data. Variant chr17-1754359-G-A is described in ClinVar as [Benign]. Clinvar id is 256834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINF2	NM_000934.4 link	c.1301G>A	p.Arg434Lys	missense_variant	Exon 10 of 10	ENST00000453066.6	NP_000925.2	P08697-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINF2	ENST00000453066.6 link	c.1301G>A	p.Arg434Lys	missense_variant	Exon 10 of 10	5	NM_000934.4	ENSP00000402286.2		P08697-1C9JMH6

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30328

AN:

152112

Hom.:

3121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.375

Gnomad FIN

AF:

0.184

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.199

GnomAD2 exomes

AF:

0.217

AC:

54417

AN:

251348

AF XY:

0.223

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.265

Gnomad ASJ exome

AF:

0.172

Gnomad EAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.184

Gnomad NFE exome

AF:

0.183

Gnomad OTH exome

AF:

0.200

GnomAD4 exome

AF:

0.201

AC:

293746

AN:

1461820

Hom.:

31467

Cov.:

AF XY:

0.206

AC XY:

149750

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.210

AC:

7027

AN:

33480

American (AMR)

AF:

0.259

AC:

11582

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

4640

AN:

26136

East Asian (EAS)

AF:

0.151

AC:

6012

AN:

39700

South Asian (SAS)

AF:

0.374

AC:

32283

AN:

86258

European-Finnish (FIN)

AF:

0.183

AC:

9752

AN:

53370

Middle Eastern (MID)

AF:

0.254

AC:

1465

AN:

5766

European-Non Finnish (NFE)

AF:

0.188

AC:

208551

AN:

1111990

Other (OTH)

AF:

0.206

AC:

12434

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

16056

32112

48169

64225

80281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.199

AC:

30359

AN:

152230

Hom.:

3125

Cov.:

AF XY:

0.205

AC XY:

15257

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.204

AC:

8462

AN:

41532

American (AMR)

AF:

0.231

AC:

3540

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

590

AN:

3466

East Asian (EAS)

AF:

0.149

AC:

773

AN:

5174

South Asian (SAS)

AF:

0.374

AC:

1805

AN:

4820

European-Finnish (FIN)

AF:

0.184

AC:

1948

AN:

10608

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.184

AC:

12544

AN:

68020

Other (OTH)

AF:

0.204

AC:

431

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1298

2596

3893

5191

6489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.188

Hom.:

8428

Bravo

AF:

0.197

TwinsUK

AF:

0.187

AC:

695

ALSPAC

AF:

0.181

AC:

697

ESP6500AA

AF:

0.212

AC:

932

ESP6500EA

AF:

0.180

AC:

1547

ExAC

AF:

0.216

AC:

26270

Asia WGS

AF:

0.309

AC:

1072

AN:

3478

EpiCase

AF:

0.185

EpiControl

AF:

0.179

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.21

T;.;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.64

T;T;.

MetaRNN

Benign

0.0024

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.93

L;.;L

PhyloP100

-0.051

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.36

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.48

T;T;T

Sift4G

Benign

0.77

T;T;T

Polyphen

0.0010

B;.;B

Vest4

0.013

MPC

0.46

ClinPred

0.00055

GERP RS

0.74

Varity_R

0.096

gMVP

0.55

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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rs1057335

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over