15-39586066-C-T

Variant names:

• chr15-39586066-C-T
• rs753598
• NM_003246.4:c.1120+503C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003246.4(THBS1):​c.1120+503C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,046 control chromosomes in the GnomAD database, including 7,345 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 0.25 (7345 hom., cov: 33)
• Consequence: THBS1 NM_003246.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• Publications: 3 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]

THBS1-IT1 (HGNC:55225): (THBS1 intronic transcript 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003246.4. 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
	THBS1	NM_003246.4	MANE Select	c.1120+503C>T		intron	N/A	NP_003237.2
	THBS1-IT1	NR_186398.1		n.-60C>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS1	ENST00000260356.6	TSL:1 MANE Select	c.1120+503C>T		intron	N/A	ENSP00000260356.5	P07996-1
	THBS1	ENST00000880750.1		c.1120+503C>T		intron	N/A	ENSP00000550809.1
	THBS1	ENST00000880751.1		c.1120+503C>T		intron	N/A	ENSP00000550810.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38025 AN: 151924 Hom.: 7319 Cov.: 33

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.235

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.251 AC: 38093 AN: 152046 Hom.: 7345 Cov.: 33 AF XY: 0.248 AC XY: 18427 AN XY: 74350

African (AFR) AF: 0.537 AC: 22232 AN: 41428

American (AMR) AF: 0.176 AC: 2698 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3464

East Asian (EAS) AF: 0.322 AC: 1662 AN: 5164

South Asian (SAS) AF: 0.206 AC: 988 AN: 4804

European-Finnish (FIN) AF: 0.104 AC: 1105 AN: 10576

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8222 AN: 67998

Other (OTH) AF: 0.234 AC: 495 AN: 2114

Alfa AF: 0.0987 Hom.: 250

Bravo AF: 0.269

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.50
PhyloP100		-0.24
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: rs753598; hg19: chr15-39878267;