chr6-169243590-C-T

Variant names:

• chr6-169243590-C-T
• rs9379341
• NM_003247.5:c.695-1632G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003247.5(THBS2):​c.695-1632G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,126 control chromosomes in the GnomAD database, including 15,509 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 0.43 (15509 hom., cov: 33)
• Consequence: THBS2 NM_003247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS2	NM_003247.5	c.695-1632G>A		intron_variant	Intron 4 of 21	ENST00000617924.6	NP_003238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS2	ENST00000617924.6	c.695-1632G>A		intron_variant	Intron 4 of 21	1	NM_003247.5	ENSP00000482784.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65580 AN: 152008 Hom.: 15502 Cov.: 33

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.431 AC: 65626 AN: 152126 Hom.: 15509 Cov.: 33 AF XY: 0.431 AC XY: 32066 AN XY: 74378

African (AFR) AF: 0.607 AC: 25187 AN: 41494

American (AMR) AF: 0.468 AC: 7152 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1033 AN: 3470

East Asian (EAS) AF: 0.646 AC: 3342 AN: 5172

South Asian (SAS) AF: 0.489 AC: 2355 AN: 4820

European-Finnish (FIN) AF: 0.278 AC: 2949 AN: 10590

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22410 AN: 67976

Other (OTH) AF: 0.396 AC: 836 AN: 2110

Alfa AF: 0.364 Hom.: 42640

Bravo AF: 0.452

Asia WGS AF: 0.533 AC: 1853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.54
PhyloP100		-0.012
Mutation Taster		=100/0	polymorphism (auto)

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: rs9379341; hg19: chr6-169643685;