7-93886765-C-T

Position:

• chr7-93886765-C-T

Variant summary

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

The NM_006528.4(TFPI2):​c.*55G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 1,120,410 control chromosomes in the GnomAD database, including 1,754 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 0.063 (473 hom., cov: 32)
  • Exomes 𝑓: 0.033 (1281 hom.)
• Consequence: TFPI2 NM_006528.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFPI2	NM_006528.4	c.*55G>A		3_prime_UTR_variant	5/5	ENST00000222543.11
TFPI2	NM_001271003.2	c.*55G>A		3_prime_UTR_variant	5/5
TFPI2	NM_001271004.2	c.*126G>A		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFPI2	ENST00000222543.11	c.*55G>A		3_prime_UTR_variant	5/5	1	NM_006528.4	P2
TFPI2	ENST00000451238.1	c.*126G>A		3_prime_UTR_variant	4/4	2
TFPI2	ENST00000650573.1	c.*55G>A		3_prime_UTR_variant	5/5			A2
GNGT1	ENST00000455502.5	c.-12+216C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0624 AC: 9492 AN: 152040 Hom.: 467 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0502

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0867

Gnomad FIN AF: 0.0252

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0192

Gnomad OTH AF: 0.0592

GnomAD4 exome AF: 0.0325 AC: 31503 AN: 968252 Hom.: 1281 Cov.: 13 AF XY: 0.0331 AC XY: 16454 AN XY: 497802

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.0474

Gnomad4 EAS exome AF: 0.205

Gnomad4 SAS exome AF: 0.0703

Gnomad4 FIN exome AF: 0.0261

Gnomad4 NFE exome AF: 0.0173

Gnomad4 OTH exome AF: 0.0390

GnomAD4 genome AF: 0.0626 AC: 9527 AN: 152158 Hom.: 473 Cov.: 32 AF XY: 0.0654 AC XY: 4867 AN XY: 74392

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.0502

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.0863

Gnomad4 FIN AF: 0.0252

Gnomad4 NFE AF: 0.0192

Gnomad4 OTH AF: 0.0591

Alfa AF: 0.0280 Hom.: 101

Bravo AF: 0.0686

Asia WGS AF: 0.163 AC: 565 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.49

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: rs4264; hg19: chr7-93516077;