7-93886681-T-G

Position:

• chr7-93886681-T-G

Variant summary

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

The NM_006528.4(TFPI2):​c.*139A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 607,298 control chromosomes in the GnomAD database, including 27,254 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 0.26 (5883 hom., cov: 32)
  • Exomes 𝑓: 0.29 (21371 hom.)
• Consequence: TFPI2 NM_006528.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFPI2	NM_006528.4	c.*139A>C		3_prime_UTR_variant	5/5	ENST00000222543.11	NP_006519.1
TFPI2	NM_001271003.2	c.*139A>C		3_prime_UTR_variant	5/5		NP_001257932.1
TFPI2	NM_001271004.2	c.*210A>C		3_prime_UTR_variant	5/5		NP_001257933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFPI2	ENST00000222543	c.*139A>C		3_prime_UTR_variant	5/5	1	NM_006528.4	ENSP00000222543.5
TFPI2	ENST00000650573	c.*139A>C		3_prime_UTR_variant	5/5			ENSP00000497131.1
TFPI2	ENST00000451238.1	c.*210A>C		3_prime_UTR_variant	4/4	2		ENSP00000416370.1
GNGT1	ENST00000455502.5	c.-12+132T>G		intron_variant		2		ENSP00000395857.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39214 AN: 151822 Hom.: 5882 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.280

GnomAD4 exome AF: 0.292 AC: 133048 AN: 455358 Hom.: 21371 Cov.: 6 AF XY: 0.296 AC XY: 71207 AN XY: 240706

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.428

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.585

Gnomad4 SAS exome AF: 0.397

Gnomad4 FIN exome AF: 0.334

Gnomad4 NFE exome AF: 0.256

Gnomad4 OTH exome AF: 0.289

GnomAD4 genome AF: 0.258 AC: 39243 AN: 151940 Hom.: 5883 Cov.: 32 AF XY: 0.269 AC XY: 19940 AN XY: 74256

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.617

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.281

Alfa AF: 0.203 Hom.: 1009

Bravo AF: 0.259

Asia WGS AF: 0.477 AC: 1647 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.2
DANN	Benign	0.90

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: rs4517; hg19: chr7-93515993;