rs4517

Variant names:

• chr7-93886681-T-A
• rs4517
• NM_006528.4:c.*139A>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006528.4(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 NM_006528.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 9 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: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006528.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFPI2	NM_006528.4	MANE Select	c.*139A>T		3_prime_UTR	Exon 5 of 5	NP_006519.1	P48307-1
	TFPI2	NM_001271003.2		c.*139A>T		3_prime_UTR	Exon 5 of 5	NP_001257932.1	P48307-2
	TFPI2	NM_001271004.2		c.*210A>T		3_prime_UTR	Exon 5 of 5	NP_001257933.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFPI2	ENST00000222543.11	TSL:1 MANE Select	c.*139A>T		3_prime_UTR	Exon 5 of 5	ENSP00000222543.5	P48307-1
	TFPI2	ENST00000650573.1		c.*139A>T		3_prime_UTR	Exon 5 of 5	ENSP00000497131.1	A0A3B3IS67
	TFPI2	ENST00000898459.1		c.*139A>T		3_prime_UTR	Exon 4 of 4	ENSP00000568518.1

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

African (AFR) AF: 0.000107 AC: 1 AN: 9374

American (AMR) AF: 0.00 AC: 0 AN: 10476

Ashkenazi Jewish (ASJ) AF: 0.0000687 AC: 1 AN: 14560

East Asian (EAS) AF: 0.00 AC: 0 AN: 24498

South Asian (SAS) AF: 0.00 AC: 0 AN: 36020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30636

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1974

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 303902

Other (OTH) AF: 0.00 AC: 0 AN: 24968

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.7
DANN	Benign	0.88
PhyloP100		0.031

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

Other links and lift over

dbSNP: rs4517; hg19: chr7-93515993;