rs2070863

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.97C>T(p.Arg33Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,553,220 control chromosomes in the GnomAD database, including 41,715 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 3590 hom., cov: 26)

Exomes 𝑓: 0.23 ( 38125 hom. )

Consequence

SERPINF2
NM_000934.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.790

Publications

62 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: Orphanet, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

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=0.004112065).

BP6

Variant 17-1745208-C-T is Benign according to our data. Variant chr17-1745208-C-T is described in ClinVar as Benign. ClinVar VariationId is 256837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000934.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINF2	NM_000934.4	MANE Select	c.97C>T	p.Arg33Trp	missense	Exon 3 of 10	NP_000925.2	P08697-1
SERPINF2	NM_001165920.1		c.97C>T	p.Arg33Trp	missense	Exon 3 of 10	NP_001159392.1	P08697-1
SERPINF2	NM_001165921.2		c.97C>T	p.Arg33Trp	missense	Exon 3 of 9	NP_001159393.1	P08697-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINF2	ENST00000453066.6	TSL:5 MANE Select	c.97C>T	p.Arg33Trp	missense	Exon 3 of 10	ENSP00000402286.2	P08697-1
SERPINF2	ENST00000382061.5	TSL:1	c.97C>T	p.Arg33Trp	missense	Exon 3 of 10	ENSP00000371493.4	P08697-1
SERPINF2	ENST00000883620.1		c.97C>T	p.Arg33Trp	missense	Exon 3 of 11	ENSP00000553679.1

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

32634

AN:

139874

Hom.:

3589

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.191

Gnomad SAS

AF:

0.403

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.232

GnomAD2 exomes

AF:

0.242

AC:

43840

AN:

180824

AF XY:

0.251

show subpopulations

Gnomad AFR exome

AF:

0.211

Gnomad AMR exome

AF:

0.274

Gnomad ASJ exome

AF:

0.194

Gnomad EAS exome

AF:

0.177

Gnomad FIN exome

AF:

0.213

Gnomad NFE exome

AF:

0.213

Gnomad OTH exome

AF:

0.227

GnomAD4 exome

AF:

0.228

AC:

321824

AN:

1413266

Hom.:

38125

Cov.:

AF XY:

0.232

AC XY:

162282

AN XY:

699172

show subpopulations

African (AFR)

AF:

0.210

AC:

6751

AN:

32184

American (AMR)

AF:

0.271

AC:

10110

AN:

37278

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

4943

AN:

25130

East Asian (EAS)

AF:

0.174

AC:

6404

AN:

36734

South Asian (SAS)

AF:

0.382

AC:

31245

AN:

81720

European-Finnish (FIN)

AF:

0.214

AC:

10570

AN:

49400

Middle Eastern (MID)

AF:

0.277

AC:

1534

AN:

5544

European-Non Finnish (NFE)

AF:

0.218

AC:

236647

AN:

1086870

Other (OTH)

AF:

0.233

AC:

13620

AN:

58406

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

15364

30728

46092

61456

76820

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8394

16788

25182

33576

41970

<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:

0.233

AC:

32651

AN:

139954

Hom.:

3590

Cov.:

AF XY:

0.241

AC XY:

16267

AN XY:

67612

show subpopulations

African (AFR)

AF:

0.227

AC:

8317

AN:

36662

American (AMR)

AF:

0.277

AC:

3758

AN:

13568

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

642

AN:

3344

East Asian (EAS)

AF:

0.191

AC:

904

AN:

4724

South Asian (SAS)

AF:

0.402

AC:

1814

AN:

4510

European-Finnish (FIN)

AF:

0.246

AC:

2178

AN:

8870

Middle Eastern (MID)

AF:

0.216

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.219

AC:

14305

AN:

65198

Other (OTH)

AF:

0.236

AC:

459

AN:

1942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1220

2440

3659

4879

6099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

364

728

1092

1456

1820

<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:

0.213

Hom.:

10105

Bravo

AF:

0.214

TwinsUK

AF:

0.223

AC:

827

ALSPAC

AF:

0.214

AC:

825

ESP6500AA

AF:

0.205

AC:

894

ESP6500EA

AF:

0.200

AC:

1705

ExAC

AF:

0.197

AC:

22950

Asia WGS

AF:

0.327

AC:

1135

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.20

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

PhyloP100

0.79

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.14

REVEL

Uncertain

0.37

Sift

Benign

0.16

Sift4G

Benign

0.069

Polyphen

0.95

Vest4

0.045

MPC

0.47

ClinPred

0.013

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.068

gMVP

0.17

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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