15-39584380-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_003246.4(THBS1):c.984C>T(p.Asn328=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00052 in 1,614,144 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00051 (4 hom.)
• Consequence: THBS1 NM_003246.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.77

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 15-39584380-C-T is Benign according to our data. Variant chr15-39584380-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 774713.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.77 with no splicing effect.
• BS2: High AC in GnomAd at 96 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THBS1	NM_003246.4	c.984C>T	p.Asn328=	synonymous_variant	6/22	ENST00000260356.6
THBS1	XM_047432980.1	c.984C>T	p.Asn328=	synonymous_variant	6/22
THBS1	XM_011521971.3	c.984C>T	p.Asn328=	synonymous_variant	6/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THBS1	ENST00000260356.6	c.984C>T	p.Asn328=	synonymous_variant	6/22	1	NM_003246.4	P1

Frequencies

GnomAD3 genomes AF: 0.000631 AC: 96 AN: 152136 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000958 AC: 241 AN: 251482 Hom.: 1 AF XY: 0.000942 AC XY: 128 AN XY: 135914

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.0190

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000193

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000509 AC: 744 AN: 1461890 Hom.: 4 Cov.: 32 AF XY: 0.000498 AC XY: 362 AN XY: 727246

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000335

Gnomad4 ASJ exome AF: 0.0180

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000132

Gnomad4 OTH exome AF: 0.00167

GnomAD4 genome AF: 0.000631 AC: 96 AN: 152254 Hom.: 0 Cov.: 33 AF XY: 0.000484 AC XY: 36 AN XY: 74452

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00176 Hom.: 1

Bravo AF: 0.000737

EpiCase AF: 0.000436

EpiControl AF: 0.000296

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.20
Dann	Benign	0.85

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: rs139530973; hg19: chr15-39876581;