rs59805398

chr7-93891949-G-C

Variant summary

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

The NR_134235.1(TFPI2-DT):n.186+870G>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,034 control chromosomes in the GnomAD database, including 6,306 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 0.27 (6306 hom., cov: 32)
• Consequence: TFPI2-DT NR_134235.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469

Genes affected

TFPI2-DT (HGNC:40581): (TFPI2 divergent transcript)

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFPI2-DT	NR_134235.1	n.186+870G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFPI2-DT	ENST00000435257.1	n.167+870G>C		intron_variant, non_coding_transcript_variant		2
GNGT1	ENST00000455502.5	c.-12+5400G>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41386 AN: 151916 Hom.: 6302 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.297

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.272 AC: 41416 AN: 152034 Hom.: 6306 Cov.: 32 AF XY: 0.283 AC XY: 21004 AN XY: 74322

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.612

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.299

Alfa AF: 0.257 Hom.: 642

Bravo AF: 0.275

Asia WGS AF: 0.472 AC: 1640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.96
Dann	Benign	0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs59805398; hg19: chr7-93521261;