rs7170682

chr15-39584211-C-T

Variant summary

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

The NM_003246.4(THBS1):c.903+24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,613,628 control chromosomes in the GnomAD database, including 25,753 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 0.24 (6466 hom., cov: 33)
  • Exomes 𝑓: 0.14 (19287 hom.)
• Consequence: THBS1 NM_003246.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

Genes affected

THBS1 (HGNC:11785): (thrombospondin 1) The protein encoded by this gene is a subunit of a disulfide-linked homotrimeric protein. This protein is an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein can bind to fibrinogen, fibronectin, laminin, type V collagen and integrins alpha-V/beta-1. This protein has been shown to play roles in platelet aggregation, angiogenesis, and tumorigenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THBS1	NM_003246.4	c.903+24C>T		intron_variant		ENST00000260356.6
THBS1	XM_011521971.3	c.903+24C>T		intron_variant
THBS1	XM_047432980.1	c.903+24C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THBS1	ENST00000260356.6	c.903+24C>T		intron_variant		1	NM_003246.4	P1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36349 AN: 152068 Hom.: 6455 Cov.: 33

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.228

GnomAD3 exomes AF: 0.167 AC: 41828 AN: 250886 Hom.: 5037 AF XY: 0.163 AC XY: 22151 AN XY: 135608

Gnomad AFR exome AF: 0.500

Gnomad AMR exome AF: 0.106

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.324

Gnomad SAS exome AF: 0.198

Gnomad FIN exome AF: 0.106

Gnomad NFE exome AF: 0.118

Gnomad OTH exome AF: 0.160

GnomAD4 exome AF: 0.144 AC: 209804 AN: 1461442 Hom.: 19287 Cov.: 33 AF XY: 0.144 AC XY: 104667 AN XY: 726950

Gnomad4 AFR exome AF: 0.516

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.344

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.123

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.239 AC: 36393 AN: 152186 Hom.: 6466 Cov.: 33 AF XY: 0.237 AC XY: 17614 AN XY: 74412

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.225

Alfa AF: 0.179 Hom.: 1054

Bravo AF: 0.256

Asia WGS AF: 0.276 AC: 963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	5.5
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs7170682; hg19: chr15-39876412; COSMIC: COSV52950077; COSMIC: COSV52950077;