rs4140885

chr2-187468337-G-A

Variant summary

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

The NM_006287.6(TFPI):c.629-405C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 151,368 control chromosomes in the GnomAD database, including 9,332 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 0.34 (9332 hom., cov: 32)
• Consequence: TFPI NM_006287.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFPI	NM_006287.6	c.629-405C>T		intron_variant		ENST00000233156.9
CALCRL-AS1	XR_007087504.1	n.3420-31169G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFPI	ENST00000233156.9	c.629-405C>T		intron_variant		1	NM_006287.6	P1
CALCRL-AS1	ENST00000412276.6	n.190-31169G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51663 AN: 151250 Hom.: 9323 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.342 AC: 51716 AN: 151368 Hom.: 9332 Cov.: 32 AF XY: 0.337 AC XY: 24925 AN XY: 73912

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.359

Alfa AF: 0.348 Hom.: 1495

Bravo AF: 0.342

Asia WGS AF: 0.259 AC: 899 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.2
Dann	Benign	0.15

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: rs4140885; hg19: chr2-188333064;