17-1745728-C-T

Variant names:

• chr17-1745728-C-T
• rs35259159
• NM_000934.4:c.186C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.289
• Publications: 5 publications found

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

ACMG classification

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINF2	NM_000934.4	MANE Select	c.186C>T	p.Ala62Ala	synonymous	Exon 5 of 10	NP_000925.2	P08697-1
	SERPINF2	NM_001165920.1		c.186C>T	p.Ala62Ala	synonymous	Exon 5 of 10	NP_001159392.1	P08697-1
	SERPINF2	NM_001165921.2		c.175+323C>T		intron	N/A	NP_001159393.1	P08697-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINF2	ENST00000453066.6	TSL:5 MANE Select	c.186C>T	p.Ala62Ala	synonymous	Exon 5 of 10	ENSP00000402286.2	P08697-1
	SERPINF2	ENST00000382061.5	TSL:1	c.186C>T	p.Ala62Ala	synonymous	Exon 5 of 10	ENSP00000371493.4	P08697-1
	SERPINF2	ENST00000883601.1		c.196C>T	p.Pro66Ser	missense	Exon 5 of 10	ENSP00000553660.1

Frequencies

GnomAD3 genomes AF: 0.0389 AC: 5919 AN: 152072 Hom.: 179 Cov.: 31

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

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.: 34 AF XY: 0.0508 AC XY: 36965 AN XY: 726984

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: 2 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: 88 AN: 5698

European-Non Finnish (NFE) AF: 0.0617 AC: 68647 AN: 1111946

Other (OTH) AF: 0.0436 AC: 2635 AN: 60378

GnomAD4 genome AF: 0.0389 AC: 5920 AN: 152190 Hom.: 179 Cov.: 31 AF XY: 0.0359 AC XY: 2674 AN XY: 74404

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: 22 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4822

European-Finnish (FIN) AF: 0.0476 AC: 505 AN: 10608

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0634 AC: 4311 AN: 67980

Other (OTH) AF: 0.0374 AC: 79 AN: 2114

Alfa AF: 0.0481 Hom.: 139

Bravo AF: 0.0368

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.0568

EpiControl AF: 0.0596

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.6
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)

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

Other links and lift over

dbSNP: rs35259159; hg19: chr17-1649022; COSMIC: COSV60665245;