chr15-39587316-C-T

Variant names:

• chr15-39587316-C-T
• rs2664141
• NM_003246.4:c.1121-31C>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.1121-31C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,592,700 control chromosomes in the GnomAD database, including 80,015 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 0.38 (13092 hom., cov: 33)
  • Exomes 𝑓: 0.30 (66923 hom.)
• Consequence: THBS1 NM_003246.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.83
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS1	NM_003246.4	MANE Select	c.1121-31C>T		intron	N/A	NP_003237.2
	THBS1-IT1	NR_186398.1		n.*63C>T		downstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS1	ENST00000260356.6	TSL:1 MANE Select	c.1121-31C>T		intron	N/A	ENSP00000260356.5
	THBS1	ENST00000466755.1	TSL:2	n.-136C>T		upstream_gene	N/A
	THBS1	ENST00000497720.1	TSL:2	n.-115C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57891 AN: 151982 Hom.: 13071 Cov.: 33

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.366

GnomAD2 exomes AF: 0.291 AC: 69374 AN: 238210 AF XY: 0.289

Gnomad AFR exome AF: 0.644

Gnomad AMR exome AF: 0.188

Gnomad ASJ exome AF: 0.277

Gnomad EAS exome AF: 0.333

Gnomad FIN exome AF: 0.218

Gnomad NFE exome AF: 0.284

Gnomad OTH exome AF: 0.288

GnomAD4 exome AF: 0.298 AC: 429269 AN: 1440600 Hom.: 66923 Cov.: 32 AF XY: 0.296 AC XY: 211510 AN XY: 713578

African (AFR) AF: 0.652 AC: 21678 AN: 33266

American (AMR) AF: 0.200 AC: 8771 AN: 43928

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 6819 AN: 25084

East Asian (EAS) AF: 0.350 AC: 13797 AN: 39372

South Asian (SAS) AF: 0.272 AC: 22694 AN: 83386

European-Finnish (FIN) AF: 0.219 AC: 11277 AN: 51548

Middle Eastern (MID) AF: 0.324 AC: 1844 AN: 5688

European-Non Finnish (NFE) AF: 0.295 AC: 323619 AN: 1098716

Other (OTH) AF: 0.315 AC: 18770 AN: 59612

GnomAD4 genome AF: 0.381 AC: 57956 AN: 152100 Hom.: 13092 Cov.: 33 AF XY: 0.372 AC XY: 27685 AN XY: 74366

African (AFR) AF: 0.638 AC: 26455 AN: 41492

American (AMR) AF: 0.285 AC: 4362 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 946 AN: 3470

East Asian (EAS) AF: 0.330 AC: 1707 AN: 5172

South Asian (SAS) AF: 0.276 AC: 1332 AN: 4824

European-Finnish (FIN) AF: 0.215 AC: 2272 AN: 10590

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19773 AN: 67942

Other (OTH) AF: 0.363 AC: 766 AN: 2110

Alfa AF: 0.338 Hom.: 2018

Bravo AF: 0.397

Asia WGS AF: 0.323 AC: 1128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.13
DANN	Benign	0.60
PhyloP100		-2.8
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: rs2664141; hg19: chr15-39879517; COSMIC: COSV107283570; COSMIC: COSV107283570;