rs12912082

Variant names:

• chr15-39590289-C-T
• rs12912082
• NM_003246.4:c.2146-227C>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.2146-227C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,188 control chromosomes in the GnomAD database, including 1,301 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 (1301 hom., cov: 32)
• Consequence: THBS1 NM_003246.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 4 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 = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS1	NM_003246.4	c.2146-227C>T		intron_variant	Intron 13 of 21	ENST00000260356.6	NP_003237.2
THBS1	XM_047432980.1	c.2146-227C>T		intron_variant	Intron 13 of 21		XP_047288936.1
THBS1	XM_011521971.3	c.1972-227C>T		intron_variant	Intron 12 of 20		XP_011520273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS1	ENST00000260356.6	c.2146-227C>T		intron_variant	Intron 13 of 21	1	NM_003246.4	ENSP00000260356.5
FSIP1	ENST00000642527.1	n.*215-1715G>A		intron_variant	Intron 3 of 3			ENSP00000496642.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18340 AN: 152068 Hom.: 1305 Cov.: 32

Gnomad AFR AF: 0.0822

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.120 AC: 18330 AN: 152188 Hom.: 1301 Cov.: 32 AF XY: 0.123 AC XY: 9154 AN XY: 74398

African (AFR) AF: 0.0821 AC: 3409 AN: 41502

American (AMR) AF: 0.134 AC: 2053 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 463 AN: 3472

East Asian (EAS) AF: 0.323 AC: 1671 AN: 5166

South Asian (SAS) AF: 0.205 AC: 987 AN: 4820

European-Finnish (FIN) AF: 0.105 AC: 1112 AN: 10602

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8147 AN: 68010

Other (OTH) AF: 0.135 AC: 284 AN: 2110

Alfa AF: 0.108 Hom.: 153

Bravo AF: 0.122

Asia WGS AF: 0.251 AC: 877 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	0.46
DANN	Benign	0.38
PhyloP100		-1.3
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: rs12912082; hg19: chr15-39882490;