rs8089

chr6-169217631-A-Cchr6-169217631-A-T

Variant summary

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

The NM_003247.5(THBS2):c.*191T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 545,236 control chromosomes in the GnomAD database, including 13,710 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 0.22 (3783 hom., cov: 33)
  • Exomes 𝑓: 0.22 (9927 hom.)
• Consequence: THBS2 NM_003247.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401

Genes affected

THBS2 (HGNC:11786): (thrombospondin 2) The protein encoded by this gene belongs to the thrombospondin family. It is a disulfide-linked homotrimeric glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein has been shown to function as a potent inhibitor of tumor growth and angiogenesis. Studies of the mouse counterpart suggest that this protein may modulate the cell surface properties of mesenchymal cells and be involved in cell adhesion and migration. [provided by RefSeq, Jul 2008]

THBS2-AS1 (HGNC:56059): (THBS2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THBS2	NM_003247.5	c.*191T>G		3_prime_UTR_variant	22/22	ENST00000617924.6
THBS2-AS1	NR_134621.1	n.681+3144A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THBS2	ENST00000617924.6	c.*191T>G		3_prime_UTR_variant	22/22	1	NM_003247.5	P4
THBS2-AS1	ENST00000660724.1	n.639+3144A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32792 AN: 151980 Hom.: 3780 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.0988

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.215 AC: 84596 AN: 393138 Hom.: 9927 Cov.: 5 AF XY: 0.212 AC XY: 43210 AN XY: 204294

Gnomad4 AFR exome AF: 0.213

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.268

Gnomad4 EAS exome AF: 0.0949

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.163

Gnomad4 NFE exome AF: 0.247

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.216 AC: 32811 AN: 152098 Hom.: 3783 Cov.: 33 AF XY: 0.211 AC XY: 15660 AN XY: 74352

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.0989

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.229

Alfa AF: 0.240 Hom.: 5835

Bravo AF: 0.219

Asia WGS AF: 0.109 AC: 383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.6
Dann	Benign	0.48

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: rs8089; hg19: chr6-169617726; COSMIC: COSV64681813;