rs13427829

Positions:

• chr2-187539556-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.-3+14644C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,122 control chromosomes in the GnomAD database, including 2,647 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 0.17 (2647 hom., cov: 32)
• Consequence: TFPI NM_006287.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFPI	NM_006287.6	c.-3+14644C>T		intron_variant		ENST00000233156.9
CALCRL-AS1	XR_007087504.1	n.3520-7173G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFPI	ENST00000233156.9	c.-3+14644C>T		intron_variant		1	NM_006287.6	P1
CALCRL-AS1	ENST00000412276.6	n.290-7173G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25124 AN: 152004 Hom.: 2645 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.0992

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.0928

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.165 AC: 25150 AN: 152122 Hom.: 2647 Cov.: 32 AF XY: 0.169 AC XY: 12567 AN XY: 74374

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.0992

Gnomad4 NFE AF: 0.0929

Gnomad4 OTH AF: 0.166

Alfa AF: 0.115 Hom.: 1233

Bravo AF: 0.177

Asia WGS AF: 0.255 AC: 888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13427829; hg19: chr2-188404283;