rs13427829

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.42
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
TFPINM_006287.6 linkuse as main transcriptc.-3+14644C>T intron_variant ENST00000233156.9
CALCRL-AS1XR_007087504.1 linkuse as main transcriptn.3520-7173G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TFPIENST00000233156.9 linkuse as main transcriptc.-3+14644C>T intron_variant 1 NM_006287.6 P1P10646-1
CALCRL-AS1ENST00000412276.6 linkuse as main transcriptn.290-7173G>A intron_variant, non_coding_transcript_variant 5

Frequencies

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs13427829; hg19: chr2-188404283; API