7-93889174-C-T

Variant names:

• chr7-93889174-C-T
• rs34489123
• NM_006528.4:c.321G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006528.4(TFPI2):​c.321G>A​(p.Glu107Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0349 in 1,609,900 control chromosomes in the GnomAD database, including 2,309 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 0.061 (451 hom., cov: 32)
  • Exomes 𝑓: 0.032 (1858 hom.)
• Consequence: TFPI2 NM_006528.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691
• Publications: 13 publications found

Genes affected

TFPI2 (HGNC:11761): (tissue factor pathway inhibitor 2) This gene encodes a member of the Kunitz-type serine proteinase inhibitor family. The protein can inhibit a variety of serine proteases including factor VIIa/tissue factor, factor Xa, plasmin, trypsin, chymotryspin and plasma kallikrein. This gene has been identified as a tumor suppressor gene in several types of cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

GNGT1 (HGNC:4411): (G protein subunit gamma transducin 1) This gene encodes the gamma subunit of transducin, a guanine nucleotide-binding protein (G protein) that is found in rod outer segments. Transducin, also known as GMPase, mediates the activation of a cyclic GTP-specific (guanosine monophosphate) phosphodiesterase by rhodopsin. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-0.691 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFPI2	NM_006528.4	c.321G>A	p.Glu107Glu	synonymous_variant	Exon 3 of 5	ENST00000222543.11	NP_006519.1
TFPI2	NM_001271003.2	c.288G>A	p.Glu96Glu	synonymous_variant	Exon 3 of 5		NP_001257932.1
TFPI2	NM_001271004.2	c.321G>A	p.Glu107Glu	synonymous_variant	Exon 3 of 5		NP_001257933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFPI2	ENST00000222543.11	c.321G>A	p.Glu107Glu	synonymous_variant	Exon 3 of 5	1	NM_006528.4	ENSP00000222543.5

Frequencies

GnomAD3 genomes AF: 0.0608 AC: 9251 AN: 152064 Hom.: 448 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.0861

Gnomad FIN AF: 0.0259

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0193

Gnomad OTH AF: 0.0584

GnomAD2 exomes AF: 0.0582 AC: 14366 AN: 246830 AF XY: 0.0546

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.0463

Gnomad EAS exome AF: 0.171

Gnomad FIN exome AF: 0.0280

Gnomad NFE exome AF: 0.0209

Gnomad OTH exome AF: 0.0482

GnomAD4 exome AF: 0.0321 AC: 46851 AN: 1457718 Hom.: 1858 Cov.: 31 AF XY: 0.0329 AC XY: 23822 AN XY: 724760

African (AFR) AF: 0.105 AC: 3485 AN: 33220

American (AMR) AF: 0.110 AC: 4850 AN: 43920

Ashkenazi Jewish (ASJ) AF: 0.0484 AC: 1260 AN: 26056

East Asian (EAS) AF: 0.201 AC: 7946 AN: 39482

South Asian (SAS) AF: 0.0740 AC: 6298 AN: 85150

European-Finnish (FIN) AF: 0.0272 AC: 1450 AN: 53380

Middle Eastern (MID) AF: 0.0382 AC: 220 AN: 5760

European-Non Finnish (NFE) AF: 0.0170 AC: 18925 AN: 1110484

Other (OTH) AF: 0.0401 AC: 2417 AN: 60266

GnomAD4 genome AF: 0.0609 AC: 9271 AN: 152182 Hom.: 451 Cov.: 32 AF XY: 0.0637 AC XY: 4738 AN XY: 74398

African (AFR) AF: 0.105 AC: 4378 AN: 41498

American (AMR) AF: 0.109 AC: 1668 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0510 AC: 177 AN: 3470

East Asian (EAS) AF: 0.172 AC: 889 AN: 5180

South Asian (SAS) AF: 0.0858 AC: 413 AN: 4814

European-Finnish (FIN) AF: 0.0259 AC: 275 AN: 10602

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0193 AC: 1312 AN: 68004

Other (OTH) AF: 0.0583 AC: 123 AN: 2110

Alfa AF: 0.0279 Hom.: 52

Bravo AF: 0.0667

Asia WGS AF: 0.166 AC: 578 AN: 3478

EpiCase AF: 0.0219

EpiControl AF: 0.0227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.67
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs34489123; hg19: chr7-93518486; COSMIC: COSV55991934; COSMIC: COSV55991934;