chr11-46719945-C-T

Position:

• chr11-46719945-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000311907.10(F2):​c.240+83C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,503,966 control chromosomes in the GnomAD database, including 24,471 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2402 hom., cov: 32)
  • Exomes 𝑓: 0.16 (22069 hom.)
• Consequence: F2 ENST00000311907.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.148

Genes affected

F2 (HGNC:3535): (coagulation factor II, thrombin) This gene encodes the prothrombin protein (also known as coagulation factor II). This protein is proteolytically cleaved in multiple steps to form the activated serine protease thrombin. The activated thrombin enzyme plays an important role in thrombosis and hemostasis by converting fibrinogen to fibrin during blood clot formation, by stimulating platelet aggregation, and by activating additional coagulation factors. Thrombin also plays a role in cell proliferation, tissue repair, and angiogenesis as well as maintaining vascular integrity during development and postnatal life. Peptides derived from the C-terminus of this protein have antimicrobial activity against E. coli and P. aeruginosa. Mutations in this gene lead to various forms of thrombosis and dysprothrombinemia. Rapid increases in cytokine levels following coronavirus infections can dysregulate the coagulation cascade and produce thrombosis, compromised blood supply, and organ failure. [provided by RefSeq, May 2020]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-46719945-C-T is Benign according to our data. Variant chr11-46719945-C-T is described in ClinVar as [Benign]. Clinvar id is 1277924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F2	NM_000506.5	c.240+83C>T		intron_variant		ENST00000311907.10	NP_000497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F2	ENST00000311907.10	c.240+83C>T		intron_variant		1	NM_000506.5	ENSP00000308541	P1
F2	ENST00000442468.1	c.210+83C>T		intron_variant		3		ENSP00000387413
F2	ENST00000530231.5	c.240+83C>T		intron_variant		5		ENSP00000433907
F2	ENST00000469189.1	n.363C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21993 AN: 152094 Hom.: 2389 Cov.: 32

Gnomad AFR AF: 0.0474

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.0796

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.158 AC: 214252 AN: 1351754 Hom.: 22069 Cov.: 25 AF XY: 0.159 AC XY: 106417 AN XY: 668400

Gnomad4 AFR exome AF: 0.0387

Gnomad4 AMR exome AF: 0.361

Gnomad4 ASJ exome AF: 0.0771

Gnomad4 EAS exome AF: 0.571

Gnomad4 SAS exome AF: 0.207

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.145 AC: 22010 AN: 152212 Hom.: 2402 Cov.: 32 AF XY: 0.154 AC XY: 11463 AN XY: 74400

Gnomad4 AFR AF: 0.0473

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.0796

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.126

Alfa AF: 0.131 Hom.: 331

Bravo AF: 0.143

Asia WGS AF: 0.304 AC: 1056 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.5
DANN	Benign	0.54

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

LitVar

Other links and lift over

dbSNP: rs2070850; hg19: chr11-46741495;