rs9393165

chr6-169220152-T-Cchr6-169220152-T-G

Variant summary

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

The NM_003247.5(THBS2):c.3511+46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 1,592,622 control chromosomes in the GnomAD database, including 361,261 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 0.72 (39717 hom., cov: 31)
  • Exomes 𝑓: 0.67 (321544 hom.)
• Consequence: THBS2 NM_003247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THBS2	NM_003247.5	c.3511+46A>G		intron_variant		ENST00000617924.6
THBS2-AS1	NR_134621.1	n.681+5665T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THBS2	ENST00000617924.6	c.3511+46A>G		intron_variant		1	NM_003247.5	P4
THBS2-AS1	ENST00000660724.1	n.639+5665T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108812 AN: 151892 Hom.: 39665 Cov.: 31

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.711

GnomAD3 exomes AF: 0.669 AC: 158439 AN: 236844 Hom.: 53768 AF XY: 0.665 AC XY: 84876 AN XY: 127572

Gnomad AFR exome AF: 0.857

Gnomad AMR exome AF: 0.716

Gnomad ASJ exome AF: 0.684

Gnomad EAS exome AF: 0.498

Gnomad SAS exome AF: 0.651

Gnomad FIN exome AF: 0.627

Gnomad NFE exome AF: 0.666

Gnomad OTH exome AF: 0.671

GnomAD4 exome AF: 0.666 AC: 959320 AN: 1440612 Hom.: 321544 Cov.: 34 AF XY: 0.665 AC XY: 474899 AN XY: 714290

Gnomad4 AFR exome AF: 0.871

Gnomad4 AMR exome AF: 0.714

Gnomad4 ASJ exome AF: 0.681

Gnomad4 EAS exome AF: 0.470

Gnomad4 SAS exome AF: 0.655

Gnomad4 FIN exome AF: 0.627

Gnomad4 NFE exome AF: 0.666

Gnomad4 OTH exome AF: 0.682

GnomAD4 genome AF: 0.717 AC: 108921 AN: 152010 Hom.: 39717 Cov.: 31 AF XY: 0.715 AC XY: 53103 AN XY: 74286

Gnomad4 AFR AF: 0.858

Gnomad4 AMR AF: 0.720

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.667

Gnomad4 OTH AF: 0.709

Alfa AF: 0.681 Hom.: 36506

Bravo AF: 0.728

Asia WGS AF: 0.595 AC: 2069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.11
Dann	Benign	0.32

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: rs9393165; hg19: chr6-169620247; COSMIC: COSV64679087;