Variant rs2228262 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003246.4(THBS1):c.2099A>G(p.Asn700Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,613,160 control chromosomes in the GnomAD database, including 9,683 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.079 ( 651 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9032 hom. )

Consequence

THBS1
NM_003246.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.32

Variant links:

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 links:

FSIP1 (HGNC:21674): (fibrous sheath interacting protein 1)

FSIP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038629174).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
THBS1	NM_003246.4 linkuse as main transcript	c.2099A>G	p.Asn700Ser	missense_variant	13/22	ENST00000260356.6	NP_003237.2
THBS1	XM_047432980.1 linkuse as main transcript	c.2099A>G	p.Asn700Ser	missense_variant	13/22		XP_047288936.1
THBS1	XM_011521971.3 linkuse as main transcript	c.1925A>G	p.Asn642Ser	missense_variant	12/21		XP_011520273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THBS1	ENST00000260356.6 linkuse as main transcript	c.2099A>G	p.Asn700Ser	missense_variant	13/22	1	NM_003246.4	ENSP00000260356	P1	P07996-1
FSIP1	ENST00000642527.1 linkuse as main transcript	c.*215-1403T>C		intron_variant, NMD_transcript_variant				ENSP00000496642

Frequencies

GnomAD3 genomes

AF:

0.0795

AC:

12093

AN:

152198

Hom.:

652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0301

Gnomad AMI

AF:

0.0888

Gnomad AMR

AF:

0.0627

Gnomad ASJ

AF:

0.0582

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0520

Gnomad FIN

AF:

0.0974

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.0780

GnomAD3 exomes

AF:

0.0793

AC:

19725

AN:

248600

Hom.:

1029

AF XY:

0.0814

AC XY:

10929

AN XY:

134308

show subpopulations

Gnomad AFR exome

AF:

0.0301

Gnomad AMR exome

AF:

0.0417

Gnomad ASJ exome

AF:

0.0592

Gnomad EAS exome

AF:

0.000491

Gnomad SAS exome

AF:

0.0497

Gnomad FIN exome

AF:

0.0982

Gnomad NFE exome

AF:

0.117

Gnomad OTH exome

AF:

0.0806

GnomAD4 exome

AF:

0.106

AC:

155200

AN:

1460844

Hom.:

9032

Cov.:

AF XY:

0.105

AC XY:

76082

AN XY:

726602

show subpopulations

Gnomad4 AFR exome

AF:

0.0253

Gnomad4 AMR exome

AF:

0.0446

Gnomad4 ASJ exome

AF:

0.0572

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0523

Gnomad4 FIN exome

AF:

0.101

Gnomad4 NFE exome

AF:

0.122

Gnomad4 OTH exome

AF:

0.0914

GnomAD4 genome

AF:

0.0794

AC:

12088

AN:

152316

Hom.:

651

Cov.:

AF XY:

0.0772

AC XY:

5748

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0300

Gnomad4 AMR

AF:

0.0626

Gnomad4 ASJ

AF:

0.0582

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0516

Gnomad4 FIN

AF:

0.0974

Gnomad4 NFE

AF:

0.120

Gnomad4 OTH

AF:

0.0767

Alfa

AF:

0.103

Hom.:

2271

Bravo

AF:

0.0734

TwinsUK

AF:

0.129

AC:

480

ALSPAC

AF:

0.117

AC:

452

ESP6500AA

AF:

0.0361

AC:

159

ESP6500EA

AF:

0.114

AC:

982

ExAC

AF:

0.0808

AC:

9807

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.67

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.0039

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.5

MutationTaster

Benign

0.0000085

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.56

Sift

Uncertain

0.027

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.29

MPC

1.1

ClinPred

0.027

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.16

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over