chr6-169237424-C-T

Variant names:

• chr6-169237424-C-T
• rs9283851
• NM_003247.5:c.1301-78G>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.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
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003247.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS2	NM_003247.5	MANE Select	c.1301-78G>A		intron	N/A	NP_003238.2
	THBS2	NM_001381939.1		c.1301-78G>A		intron	N/A	NP_001368868.1	A0A7I2V585
	THBS2	NM_001381942.1		c.1070-78G>A		intron	N/A	NP_001368871.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS2	ENST00000617924.6	TSL:1 MANE Select	c.1301-78G>A		intron	N/A	ENSP00000482784.1	P35442
	THBS2	ENST00000366787.7	TSL:1	c.1301-78G>A		intron	N/A	ENSP00000355751.3	P35442
	THBS2	ENST00000649844.1		c.1316-78G>A		intron	N/A	ENSP00000497834.1	A0A3B3ITK0

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

African (AFR) AF: 0.692 AC: 22138 AN: 31978

American (AMR) AF: 0.707 AC: 29851 AN: 42196

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 14555 AN: 25612

East Asian (EAS) AF: 0.890 AC: 34714 AN: 39010

South Asian (SAS) AF: 0.593 AC: 50079 AN: 84500

European-Finnish (FIN) AF: 0.490 AC: 22852 AN: 46664

Middle Eastern (MID) AF: 0.576 AC: 3180 AN: 5518

European-Non Finnish (NFE) AF: 0.544 AC: 583089 AN: 1071206

Other (OTH) AF: 0.589 AC: 34402 AN: 58446

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

African (AFR) AF: 0.691 AC: 28685 AN: 41498

American (AMR) AF: 0.658 AC: 10055 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2069 AN: 3470

East Asian (EAS) AF: 0.898 AC: 4629 AN: 5152

South Asian (SAS) AF: 0.597 AC: 2878 AN: 4822

European-Finnish (FIN) AF: 0.487 AC: 5167 AN: 10604

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37631 AN: 67984

Other (OTH) AF: 0.633 AC: 1339 AN: 2114

Alfa AF: 0.584 Hom.: 6464

Bravo AF: 0.633

Asia WGS AF: 0.753 AC: 2615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.037
DANN	Benign	0.43
PhyloP100		-1.1
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: rs9283851; hg19: chr6-169637519;