17-1745973-A-G

Variant names:

• chr17-1745973-A-G
• rs7501729
• NM_000934.4:c.367+64A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000934.4(SERPINF2):​c.367+64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 1,555,044 control chromosomes in the GnomAD database, including 425,846 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (40494 hom., cov: 31)
  • Exomes 𝑓: 0.74 (385352 hom.)
• Consequence: SERPINF2 NM_000934.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.679
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 17-1745973-A-G is Benign according to our data. Variant chr17-1745973-A-G is described in ClinVar as Benign. ClinVar VariationId is 1282784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 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.367+64A>G		intron	N/A	NP_000925.2	P08697-1
	SERPINF2	NM_001165920.1		c.367+64A>G		intron	N/A	NP_001159392.1	P08697-1
	SERPINF2	NM_001165921.2		c.175+568A>G		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.367+64A>G		intron	N/A	ENSP00000402286.2	P08697-1
	SERPINF2	ENST00000382061.5	TSL:1	c.367+64A>G		intron	N/A	ENSP00000371493.4	P08697-1
	SERPINF2	ENST00000883634.1		c.431A>G	p.Asn144Ser	missense	Exon 5 of 10	ENSP00000553693.1

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110868 AN: 151892 Hom.: 40452 Cov.: 31

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.710

GnomAD4 exome AF: 0.740 AC: 1038843 AN: 1403034 Hom.: 385352 AF XY: 0.741 AC XY: 519555 AN XY: 701280

African (AFR) AF: 0.713 AC: 22992 AN: 32234

American (AMR) AF: 0.693 AC: 30936 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 17060 AN: 25768

East Asian (EAS) AF: 0.859 AC: 33855 AN: 39396

South Asian (SAS) AF: 0.768 AC: 65355 AN: 85152

European-Finnish (FIN) AF: 0.740 AC: 39069 AN: 52770

Middle Eastern (MID) AF: 0.680 AC: 3850 AN: 5660

European-Non Finnish (NFE) AF: 0.739 AC: 782586 AN: 1058896

Other (OTH) AF: 0.737 AC: 43140 AN: 58526

GnomAD4 genome AF: 0.730 AC: 110965 AN: 152010 Hom.: 40494 Cov.: 31 AF XY: 0.730 AC XY: 54196 AN XY: 74276

African (AFR) AF: 0.714 AC: 29613 AN: 41462

American (AMR) AF: 0.705 AC: 10759 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2297 AN: 3468

East Asian (EAS) AF: 0.855 AC: 4416 AN: 5162

South Asian (SAS) AF: 0.761 AC: 3667 AN: 4818

European-Finnish (FIN) AF: 0.738 AC: 7796 AN: 10560

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 49989 AN: 67962

Other (OTH) AF: 0.713 AC: 1504 AN: 2108

Alfa AF: 0.676 Hom.: 2839

Bravo AF: 0.725

Asia WGS AF: 0.824 AC: 2864 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	10
DANN	Benign	0.65
PhyloP100		0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7501729; hg19: chr17-1649267; COSMIC: COSV60663831;