chr2-187503148-A-G

Variant names:

• chr2-187503148-A-G
• rs2300412
• NM_006287.6:c.121+500T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006287.6(TFPI):​c.121+500T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 151,628 control chromosomes in the GnomAD database, including 24,584 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 0.55 (24584 hom., cov: 30)
• Consequence: TFPI NM_006287.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006287.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFPI	NM_006287.6	MANE Select	c.121+500T>C		intron	N/A	NP_006278.1
	TFPI	NM_001329239.2		c.121+500T>C		intron	N/A	NP_001316168.1
	TFPI	NM_001329240.2		c.121+500T>C		intron	N/A	NP_001316169.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFPI	ENST00000233156.9	TSL:1 MANE Select	c.121+500T>C		intron	N/A	ENSP00000233156.3
	TFPI	ENST00000339091.8	TSL:1	c.121+500T>C		intron	N/A	ENSP00000342306.4
	TFPI	ENST00000409676.5	TSL:1	c.121+500T>C		intron	N/A	ENSP00000386344.1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83835 AN: 151508 Hom.: 24584 Cov.: 30

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.553 AC: 83854 AN: 151628 Hom.: 24584 Cov.: 30 AF XY: 0.558 AC XY: 41309 AN XY: 74056

African (AFR) AF: 0.344 AC: 14214 AN: 41330

American (AMR) AF: 0.616 AC: 9363 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2200 AN: 3472

East Asian (EAS) AF: 0.798 AC: 4105 AN: 5142

South Asian (SAS) AF: 0.586 AC: 2820 AN: 4812

European-Finnish (FIN) AF: 0.666 AC: 6959 AN: 10450

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.624 AC: 42355 AN: 67920

Other (OTH) AF: 0.558 AC: 1171 AN: 2098

Alfa AF: 0.594 Hom.: 9278

Bravo AF: 0.546

Asia WGS AF: 0.643 AC: 2239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.094
DANN	Benign	0.72
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2300412; hg19: chr2-188367875;