chr17-1745341-C-T

Variant names:

• chr17-1745341-C-T
• rs185025710
• NM_000934.4:c.111C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_000934.4(SERPINF2):​c.111C>T​(p.Ser37Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00046 in 1,612,642 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00077 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00043 (4 hom.)
• Consequence: SERPINF2 NM_000934.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.06
• Publications: 1 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-1745341-C-T is Benign according to our data. Variant chr17-1745341-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 731846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.06 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR,AD gene

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.111C>T	p.Ser37Ser	synonymous	Exon 4 of 10	NP_000925.2	P08697-1
	SERPINF2	NM_001165920.1		c.111C>T	p.Ser37Ser	synonymous	Exon 4 of 10	NP_001159392.1	P08697-1
	SERPINF2	NM_001165921.2		c.111C>T	p.Ser37Ser	synonymous	Exon 4 of 9	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.111C>T	p.Ser37Ser	synonymous	Exon 4 of 10	ENSP00000402286.2	P08697-1
	SERPINF2	ENST00000382061.5	TSL:1	c.111C>T	p.Ser37Ser	synonymous	Exon 4 of 10	ENSP00000371493.4	P08697-1
	SERPINF2	ENST00000883620.1		c.111C>T	p.Ser37Ser	synonymous	Exon 4 of 11	ENSP00000553679.1

Frequencies

GnomAD3 genomes AF: 0.000766 AC: 116 AN: 151508 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000461

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0162

Gnomad SAS AF: 0.00167

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00154 AC: 385 AN: 250546 AF XY: 0.00147

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.000521

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.0169

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.000982

GnomAD4 exome AF: 0.000428 AC: 626 AN: 1461018 Hom.: 4 Cov.: 43 AF XY: 0.000425 AC XY: 309 AN XY: 726802

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.000537 AC: 24 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00214 AC: 56 AN: 26130

East Asian (EAS) AF: 0.00879 AC: 349 AN: 39688

South Asian (SAS) AF: 0.000487 AC: 42 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52838

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5728

European-Non Finnish (NFE) AF: 0.0000729 AC: 81 AN: 1111846

Other (OTH) AF: 0.00118 AC: 71 AN: 60354

GnomAD4 genome AF: 0.000765 AC: 116 AN: 151624 Hom.: 0 Cov.: 28 AF XY: 0.000891 AC XY: 66 AN XY: 74098

African (AFR) AF: 0.0000242 AC: 1 AN: 41368

American (AMR) AF: 0.000460 AC: 7 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3462

East Asian (EAS) AF: 0.0162 AC: 83 AN: 5120

South Asian (SAS) AF: 0.00167 AC: 8 AN: 4782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67862

Other (OTH) AF: 0.00143 AC: 3 AN: 2102

Alfa AF: 0.000327 Hom.: 1

Bravo AF: 0.000763

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	SERPINF2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.50
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs185025710; hg19: chr17-1648635; COSMIC: COSV60665093;