Variant chr17-1745000-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000934.4(SERPINF2):c.5C>T(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,613,214 control chromosomes in the GnomAD database, including 39,047 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.22 ( 3540 hom., cov: 30)

Exomes 𝑓: 0.22 ( 35507 hom. )

Consequence

SERPINF2
NM_000934.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.488

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001448214).

BP6

Variant 17-1745000-C-T is Benign according to our data. Variant chr17-1745000-C-T is described in ClinVar as [Benign]. Clinvar id is 256836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINF2	NM_000934.4 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	2/10	ENST00000453066.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINF2	ENST00000453066.6 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	2/10	5	NM_000934.4	P1	P08697-1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32669

AN:

151740

Hom.:

3536

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.0998

Gnomad AMR

AF:

0.208

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.170

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.194

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.192

GnomAD3 exomes

AF:

0.202

AC:

50613

AN:

250204

Hom.:

5338

AF XY:

0.197

AC XY:

26748

AN XY:

135536

show subpopulations

Gnomad AFR exome

AF:

0.234

Gnomad AMR exome

AF:

0.217

Gnomad ASJ exome

AF:

0.137

Gnomad EAS exome

AF:

0.176

Gnomad SAS exome

AF:

0.117

Gnomad FIN exome

AF:

0.197

Gnomad NFE exome

AF:

0.227

Gnomad OTH exome

AF:

0.204

GnomAD4 exome

AF:

0.218

AC:

318585

AN:

1461356

Hom.:

35507

Cov.:

AF XY:

0.215

AC XY:

156267

AN XY:

726966

show subpopulations

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.217

Gnomad4 ASJ exome

AF:

0.141

Gnomad4 EAS exome

AF:

0.170

Gnomad4 SAS exome

AF:

0.121

Gnomad4 FIN exome

AF:

0.204

Gnomad4 NFE exome

AF:

0.231

Gnomad4 OTH exome

AF:

0.203

GnomAD4 genome

AF:

0.215

AC:

32704

AN:

151858

Hom.:

3540

Cov.:

AF XY:

0.210

AC XY:

15563

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.233

Gnomad4 AMR

AF:

0.208

Gnomad4 ASJ

AF:

0.132

Gnomad4 EAS

AF:

0.170

Gnomad4 SAS

AF:

0.118

Gnomad4 FIN

AF:

0.194

Gnomad4 NFE

AF:

0.227

Gnomad4 OTH

AF:

0.191

Alfa

AF:

0.217

Hom.:

7427

Bravo

AF:

0.221

TwinsUK

AF:

0.264

AC:

979

ALSPAC

AF:

0.238

AC:

919

ESP6500AA

AF:

0.242

AC:

1065

ESP6500EA

AF:

0.221

AC:

1902

ExAC

AF:

0.206

AC:

24982

Asia WGS

AF:

0.158

AC:

553

AN:

3478

EpiCase

AF:

0.210

EpiControl

AF:

0.216

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.20

.;T;.;.;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.50

T;T;T;T;.

MetaRNN

Benign

0.0014

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;N;N;.;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.97

N;N;N;N;N

REVEL

Benign

0.27

Sift

Benign

0.30

T;T;T;D;T

Sift4G

Benign

0.30

T;T;T;T;T

Polyphen

0.0030

.;B;.;.;B

Vest4

0.050, 0.11, 0.053

MPC

0.45

ClinPred

0.0091

GERP RS

-0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.069

gMVP

0.20

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over