rs1478604

Positions:

• chr15-39581120-T-C

Variant summary

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

The NM_003246.4(THBS1):​c.-138T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,698 control chromosomes in the GnomAD database, including 14,649 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 0.40 (14620 hom., cov: 33)
  • Exomes 𝑓: 0.28 (29 hom.)
• Consequence: THBS1 NM_003246.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THBS1	NM_003246.4	c.-138T>C		5_prime_UTR_variant	1/22	ENST00000260356.6	NP_003237.2
THBS1	XM_047432980.1	c.-259T>C		5_prime_UTR_variant	1/22		XP_047288936.1
THBS1	XM_011521971.3	c.-138T>C		5_prime_UTR_variant	1/21		XP_011520273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THBS1	ENST00000260356	c.-138T>C		5_prime_UTR_variant	1/22	1	NM_003246.4	ENSP00000260356.5
THBS1	ENST00000397591	c.-259T>C		5_prime_UTR_variant	1/3	2		ENSP00000380720.2

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60345 AN: 151996 Hom.: 14591 Cov.: 33

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.375

GnomAD4 exome AF: 0.280 AC: 164 AN: 586 Hom.: 29 Cov.: 0 AF XY: 0.316 AC XY: 100 AN XY: 316

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.264

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.339

Gnomad4 OTH exome AF: 0.313

GnomAD4 genome AF: 0.397 AC: 60419 AN: 152112 Hom.: 14620 Cov.: 33 AF XY: 0.388 AC XY: 28874 AN XY: 74386

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.371

Alfa AF: 0.307 Hom.: 9964

Bravo AF: 0.416

Asia WGS AF: 0.325 AC: 1134 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.7
DANN	Benign	0.52

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: rs1478604; hg19: chr15-39873321;