rs7594359

chr2-187544121-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006287.6(TFPI):c.-3+10079G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,958 control chromosomes in the GnomAD database, including 10,871 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10871 hom., cov: 32)
• Consequence: TFPI NM_006287.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330

Genes affected

TFPI (HGNC:11760): (tissue factor pathway inhibitor) This gene encodes a Kunitz-type serine protease inhibitor that regulates the tissue factor (TF)-dependent pathway of blood coagulation. The coagulation process initiates with the formation of a factor VIIa-TF complex, which proteolytically activates additional proteases (factors IX and X) and ultimately leads to the formation of a fibrin clot. The product of this gene inhibits the activated factor X and VIIa-TF proteases in an autoregulatory loop. Inhibition of the encoded protein restores hemostasis in animal models of hemophilia. This gene encodes multiple protein isoforms that differ in their inhibitory activity, specificity and cellular localization. [provided by RefSeq, Jul 2016]

CALCRL-AS1 (HGNC:55863): (CALCRL and TFPI antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFPI	NM_006287.6	c.-3+10079G>A		intron_variant		ENST00000233156.9
CALCRL-AS1	XR_007087504.1	n.3520-2608C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFPI	ENST00000233156.9	c.-3+10079G>A		intron_variant		1	NM_006287.6	P1
CALCRL-AS1	ENST00000412276.6	n.290-2608C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54992 AN: 151840 Hom.: 10876 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.389

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.362 AC: 54984 AN: 151958 Hom.: 10871 Cov.: 32 AF XY: 0.355 AC XY: 26339 AN XY: 74276

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.385

Alfa AF: 0.413 Hom.: 2757

Bravo AF: 0.362

Asia WGS AF: 0.273 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.5
Dann	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7594359; hg19: chr2-188408848;