17-1754605-G-T

Variant names:

• chr17-1754605-G-T
• rs1057355
• NM_000934.4:c.*71G>T

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.*71G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 1,554,712 control chromosomes in the GnomAD database, including 170,277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17160 hom., cov: 29)
  • Exomes 𝑓: 0.47 (153117 hom.)
• Consequence: SERPINF2 NM_000934.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.355
• Publications: 15 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-1754605-G-T is Benign according to our data. Variant chr17-1754605-G-T is described in ClinVar as Benign. ClinVar VariationId is 1291982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINF2	NM_000934.4	c.*71G>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000453066.6	NP_000925.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINF2	ENST00000453066.6	c.*71G>T		3_prime_UTR_variant	Exon 10 of 10	5	NM_000934.4	ENSP00000402286.2
SERPINF2	ENST00000382061.5	c.*71G>T		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000371493.4
SERPINF2	ENST00000324015.7	c.*71G>T		3_prime_UTR_variant	Exon 10 of 10	5		ENSP00000321853.3
SERPINF2	ENST00000450523.6	c.*71G>T		3_prime_UTR_variant	Exon 9 of 9	2		ENSP00000403877.2

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71622 AN: 151292 Hom.: 17136 Cov.: 29

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.457

GnomAD4 exome AF: 0.466 AC: 653254 AN: 1403302 Hom.: 153117 Cov.: 29 AF XY: 0.467 AC XY: 325386 AN XY: 697034

African (AFR) AF: 0.528 AC: 16819 AN: 31864

American (AMR) AF: 0.537 AC: 20086 AN: 37430

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 8410 AN: 23380

East Asian (EAS) AF: 0.406 AC: 15999 AN: 39422

South Asian (SAS) AF: 0.533 AC: 42547 AN: 79806

European-Finnish (FIN) AF: 0.432 AC: 16100 AN: 37244

Middle Eastern (MID) AF: 0.411 AC: 2272 AN: 5530

European-Non Finnish (NFE) AF: 0.462 AC: 504148 AN: 1090216

Other (OTH) AF: 0.460 AC: 26873 AN: 58410

GnomAD4 genome AF: 0.474 AC: 71694 AN: 151410 Hom.: 17160 Cov.: 29 AF XY: 0.474 AC XY: 35058 AN XY: 73940

African (AFR) AF: 0.529 AC: 21804 AN: 41234

American (AMR) AF: 0.493 AC: 7484 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1202 AN: 3470

East Asian (EAS) AF: 0.410 AC: 2094 AN: 5104

South Asian (SAS) AF: 0.531 AC: 2549 AN: 4798

European-Finnish (FIN) AF: 0.417 AC: 4361 AN: 10462

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.454 AC: 30779 AN: 67852

Other (OTH) AF: 0.463 AC: 977 AN: 2110

Alfa AF: 0.448 Hom.: 21632

Bravo AF: 0.479

Asia WGS AF: 0.532 AC: 1849 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.87
DANN	Benign	0.75
PhyloP100		-0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs1057355; hg19: chr17-1657899; COSMIC: COSV60663897; COSMIC: COSV60663897;