6-169237424-C-T

Variant names:

• chr6-169237424-C-T
• rs9283851
• NM_003247.5:c.1301-78G>A

Variant summary

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

The NM_003247.5(THBS2):​c.1301-78G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,557,268 control chromosomes in the GnomAD database, including 257,987 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 0.61 (29309 hom., cov: 34)
  • Exomes 𝑓: 0.57 (228678 hom.)
• Consequence: THBS2 NM_003247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS2	NM_003247.5	c.1301-78G>A		intron_variant	Intron 8 of 21	ENST00000617924.6	NP_003238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS2	ENST00000617924.6	c.1301-78G>A		intron_variant	Intron 8 of 21	1	NM_003247.5	ENSP00000482784.1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93179 AN: 152020 Hom.: 29259 Cov.: 34

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.632

GnomAD4 exome AF: 0.566 AC: 794860 AN: 1405130 Hom.: 228678 Cov.: 24 AF XY: 0.566 AC XY: 396237 AN XY: 700422

Gnomad4 AFR exome AF: 0.692

Gnomad4 AMR exome AF: 0.707

Gnomad4 ASJ exome AF: 0.568

Gnomad4 EAS exome AF: 0.890

Gnomad4 SAS exome AF: 0.593

Gnomad4 FIN exome AF: 0.490

Gnomad4 NFE exome AF: 0.544

Gnomad4 OTH exome AF: 0.589

GnomAD4 genome AF: 0.613 AC: 93285 AN: 152138 Hom.: 29309 Cov.: 34 AF XY: 0.611 AC XY: 45440 AN XY: 74384

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.633

Alfa AF: 0.581 Hom.: 6264

Bravo AF: 0.633

Asia WGS AF: 0.753 AC: 2615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.037
DANN	Benign	0.43

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: rs9283851; hg19: chr6-169637519;