rs3743125

Variant names:

• chr15-39595647-G-A
• rs3743125
• NM_003246.4:c.*278G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
THBS1	NM_003246.4	c.*278G>A		3_prime_UTR_variant	Exon 22 of 22	ENST00000260356.6	NP_003237.2
THBS1	XM_047432980.1	c.*278G>A		3_prime_UTR_variant	Exon 22 of 22		XP_047288936.1
THBS1	XM_011521971.3	c.*278G>A		3_prime_UTR_variant	Exon 21 of 21		XP_011520273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS1	ENST00000260356.6	c.*278G>A		3_prime_UTR_variant	Exon 22 of 22	1	NM_003246.4	ENSP00000260356.5

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

GnomAD2 exomes AF: 0.144 AC: 18849 AN: 130680 AF XY: 0.150

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 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

African (AFR) AF: 0.0860 AC: 1153 AN: 13406

American (AMR) AF: 0.0962 AC: 3004 AN: 31212

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 2221 AN: 16592

East Asian (EAS) AF: 0.338 AC: 7829 AN: 23160

South Asian (SAS) AF: 0.196 AC: 11880 AN: 60614

European-Finnish (FIN) AF: 0.107 AC: 2409 AN: 22552

Middle Eastern (MID) AF: 0.213 AC: 731 AN: 3432

European-Non Finnish (NFE) AF: 0.121 AC: 30112 AN: 249830

Other (OTH) AF: 0.144 AC: 3468 AN: 24120

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

African (AFR) AF: 0.0825 AC: 3423 AN: 41508

American (AMR) AF: 0.135 AC: 2068 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 467 AN: 3472

East Asian (EAS) AF: 0.313 AC: 1621 AN: 5176

South Asian (SAS) AF: 0.206 AC: 996 AN: 4824

European-Finnish (FIN) AF: 0.105 AC: 1117 AN: 10592

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8186 AN: 68006

Other (OTH) AF: 0.136 AC: 287 AN: 2112

Alfa AF: 0.121 Hom.: 1782

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
PhyloP100		0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs3743125; hg19: chr15-39887848; COSMIC: COSV107283668; COSMIC: COSV107283668;