rs4517

Positions:

• chr7-93886681-T-A
• chr7-93886681-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000222543.11(TFPI2):​c.*139A>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 0.00000438 in 456,408 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: TFPI2 ENST00000222543.11 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFPI2	NM_006528.4	c.*139A>T		3_prime_UTR_variant	5/5	ENST00000222543.11	NP_006519.1
TFPI2	NM_001271003.2	c.*139A>T		3_prime_UTR_variant	5/5		NP_001257932.1
TFPI2	NM_001271004.2	c.*210A>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.*139A>T		3_prime_UTR_variant	5/5	1	NM_006528.4	ENSP00000222543	P2
TFPI2	ENST00000451238.1	c.*210A>T		3_prime_UTR_variant	4/4	2		ENSP00000416370
TFPI2	ENST00000650573.1	c.*139A>T		3_prime_UTR_variant	5/5			ENSP00000497131	A2
GNGT1	ENST00000455502.5	c.-12+132T>A		intron_variant		2		ENSP00000395857

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000438 AC: 2 AN: 456408 Hom.: 0 Cov.: 6 AF XY: 0.00000829 AC XY: 2 AN XY: 241226

Gnomad4 AFR exome AF: 0.000107

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000687

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.7
DANN	Benign	0.88

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;