rs4271

Positions:

• chr7-93885943-T-A

Variant summary

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

The ENST00000222543.11(TFPI2):​c.*877A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 152,132 control chromosomes in the GnomAD database, including 477 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 (477 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TFPI2 ENST00000222543.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148

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=-0.89).
• 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	Protein	UniProt
TFPI2	NM_006528.4	c.*877A>T		3_prime_UTR_variant	5/5	ENST00000222543.11	NP_006519.1
TFPI2	NM_001271003.2	c.*877A>T		3_prime_UTR_variant	5/5		NP_001257932.1
TFPI2	NM_001271004.2	c.*948A>T		3_prime_UTR_variant	5/5		NP_001257933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFPI2	ENST00000222543.11	c.*877A>T		3_prime_UTR_variant	5/5	1	NM_006528.4	ENSP00000222543	P2
GNGT1	ENST00000455502.5	c.-55-563T>A		intron_variant		2		ENSP00000395857

Frequencies

GnomAD3 genomes AF: 0.0624 AC: 9489 AN: 152014 Hom.: 471 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0502

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0863

Gnomad FIN AF: 0.0252

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0192

Gnomad OTH AF: 0.0589

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0626 AC: 9524 AN: 152132 Hom.: 477 Cov.: 32 AF XY: 0.0655 AC XY: 4869 AN XY: 74390

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.0502

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.0860

Gnomad4 FIN AF: 0.0252

Gnomad4 NFE AF: 0.0192

Gnomad4 OTH AF: 0.0588

Alfa AF: 0.0391 Hom.: 24

Bravo AF: 0.0685

Asia WGS AF: 0.161 AC: 556 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.55

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: rs4271; hg19: chr7-93515255;