Genetic Variant NM_000934.4:c.186C>T (chr17-1745728-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

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

The NM_000934.4(SERPINF2):c.186C>T(p.Ala62Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 1,613,594 control chromosomes in the GnomAD database, including 2,557 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 179 hom., cov: 31)

Exomes 𝑓: 0.052 ( 2378 hom. )

Consequence

SERPINF2
NM_000934.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.289

Publications

5 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 17-1745728-C-T is Benign according to our data. Variant chr17-1745728-C-T is described in ClinVar as Benign. ClinVar VariationId is 256835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.289 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINF2	NM_000934.4 link	c.186C>T	p.Ala62Ala	synonymous_variant	Exon 5 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.186C>T	p.Ala62Ala	synonymous_variant	Exon 5 of 10	5	NM_000934.4	ENSP00000402286.2		P08697-1C9JMH6

Frequencies

GnomAD3 genomes

AF:

0.0389

AC:

5919

AN:

152072

Hom.:

179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0105

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0346

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0476

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0634

Gnomad OTH

AF:

0.0378

GnomAD2 exomes

AF:

0.0389

AC:

9736

AN:

250460

AF XY:

0.0387

show subpopulations

Gnomad AFR exome

AF:

0.00974

Gnomad AMR exome

AF:

0.0221

Gnomad ASJ exome

AF:

0.00527

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0507

Gnomad NFE exome

AF:

0.0643

Gnomad OTH exome

AF:

0.0414

GnomAD4 exome

AF:

0.0521

AC:

76208

AN:

1461404

Hom.:

2378

Cov.:

AF XY:

0.0508

AC XY:

36965

AN XY:

726984

show subpopulations

African (AFR)

AF:

0.00675

AC:

226

AN:

33480

American (AMR)

AF:

0.0250

AC:

1116

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00635

AC:

166

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00490

AC:

423

AN:

86248

European-Finnish (FIN)

AF:

0.0547

AC:

2905

AN:

53106

Middle Eastern (MID)

AF:

0.0154

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.0617

AC:

68647

AN:

1111946

Other (OTH)

AF:

0.0436

AC:

2635

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

4174

8348

12522

16696

20870

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2370

4740

7110

9480

11850

<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:

0.0389

AC:

5920

AN:

152190

Hom.:

179

Cov.:

AF XY:

0.0359

AC XY:

2674

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0105

AC:

434

AN:

41520

American (AMR)

AF:

0.0346

AC:

529

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00634

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00311

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0476

AC:

505

AN:

10608

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0634

AC:

4311

AN:

67980

Other (OTH)

AF:

0.0374

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

276

552

829

1105

1381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0481

Hom.:

139

Bravo

AF:

0.0368

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.0568

EpiControl

AF:

0.0596

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

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.6

(source)

DANN

Benign

0.40

PhyloP100

-0.29

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over