Variant 5-80059700-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_003248.6(THBS4):c.785-3T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00855 in 1,613,980 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 12 hom., cov: 32)

Exomes 𝑓: 0.0088 ( 87 hom. )

Consequence

THBS4
NM_003248.6 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.9975

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.455

Variant links:

Genes affected

THBS4 (HGNC:11788): (thrombospondin 4) The protein encoded by this gene belongs to the thrombospondin protein family. Thrombospondin family members are adhesive glycoproteins that mediate cell-to-cell and cell-to-matrix interactions. This protein forms a pentamer and can bind to heparin and calcium. It is involved in local signaling in the developing and adult nervous system, and it contributes to spinal sensitization and neuropathic pain states. This gene is activated during the stromal response to invasive breast cancer. It may also play a role in inflammatory responses in Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

THBS4 links:

THBS4-AS1 (HGNC:40583): (THBS4 antisense RNA 1)

THBS4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 5-80059700-T-G is Benign according to our data. Variant chr5-80059700-T-G is described in ClinVar as [Benign]. Clinvar id is 3024840.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THBS4	NM_003248.6 linkuse as main transcript	c.785-3T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000350881.6	NP_003239.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
THBS4	ENST00000350881.6 linkuse as main transcript	c.785-3T>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_003248.6	ENSP00000339730	P1
THBS4-AS1	ENST00000503007.5 linkuse as main transcript	n.429-6799A>C	intron_variant, non_coding_transcript_variant	3
THBS4	ENST00000511733.1 linkuse as main transcript	c.512-3T>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2		ENSP00000422298

Frequencies

GnomAD3 genomes

AF:

0.00593

AC:

903

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00499

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0109

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00631

AC:

1586

AN:

251230

Hom.:

AF XY:

0.00605

AC XY:

821

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.000810

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.00550

Gnomad NFE exome

AF:

0.0119

Gnomad OTH exome

AF:

0.00457

GnomAD4 exome

AF:

0.00882

AC:

12897

AN:

1461678

Hom.:

Cov.:

AF XY:

0.00855

AC XY:

6216

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.00245

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000638

Gnomad4 FIN exome

AF:

0.00625

Gnomad4 NFE exome

AF:

0.0108

Gnomad4 OTH exome

AF:

0.00601

GnomAD4 genome

AF:

0.00593

AC:

903

AN:

152302

Hom.:

Cov.:

AF XY:

0.00552

AC XY:

411

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00499

Gnomad4 NFE

AF:

0.0109

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00661

Hom.:

Bravo

AF:

0.00541

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00856

EpiControl

AF:

0.00747

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

THBS4: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Benign

0.66

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.27

Position offset: 14

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over