rs3743125

Positions:

• chr15-39595647-G-A

Variant summary

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

The NM_003246.4(THBS1):​c.*278G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 597,108 control chromosomes in the GnomAD database, including 6,630 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 0.12 (1295 hom., cov: 33)
  • Exomes 𝑓: 0.14 (5335 hom.)
• Consequence: THBS1 NM_003246.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.505

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]

FSIP1 (HGNC:21674): (fibrous sheath interacting protein 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THBS1	NM_003246.4	c.*278G>A		3_prime_UTR_variant	22/22	ENST00000260356.6	NP_003237.2
THBS1	XM_047432980.1	c.*278G>A		3_prime_UTR_variant	22/22		XP_047288936.1
THBS1	XM_011521971.3	c.*278G>A		3_prime_UTR_variant	21/21		XP_011520273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THBS1	ENST00000260356.6	c.*278G>A		3_prime_UTR_variant	22/22	1	NM_003246.4	ENSP00000260356.5
FSIP1	ENST00000560769.2	n.*36-1414C>T		intron_variant		3		ENSP00000494117.1
FSIP1	ENST00000642527.1	n.*36-1414C>T		intron_variant				ENSP00000496642.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18380 AN: 152072 Hom.: 1299 Cov.: 33

Gnomad AFR AF: 0.0826

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.138

GnomAD3 exomes AF: 0.144 AC: 18849 AN: 130680 Hom.: 1701 AF XY: 0.150 AC XY: 10674 AN XY: 71108

Gnomad AFR exome AF: 0.0792

Gnomad AMR exome AF: 0.0930

Gnomad ASJ exome AF: 0.136

Gnomad EAS exome AF: 0.310

Gnomad SAS exome AF: 0.199

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.141 AC: 62807 AN: 444918 Hom.: 5335 Cov.: 3 AF XY: 0.146 AC XY: 35527 AN XY: 242570

Gnomad4 AFR exome AF: 0.0860

Gnomad4 AMR exome AF: 0.0962

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.338

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.144

GnomAD4 genome AF: 0.121 AC: 18371 AN: 152190 Hom.: 1295 Cov.: 33 AF XY: 0.123 AC XY: 9170 AN XY: 74402

Gnomad4 AFR AF: 0.0825

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.136

Alfa AF: 0.123 Hom.: 1310

Bravo AF: 0.122

Asia WGS AF: 0.247 AC: 860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	12
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3743125; hg19: chr15-39887848;