dbSNP rs404375: THBS4:c.293-2849G>A (chr5-80052936-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003248.6(THBS4):c.293-2849G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,024 control chromosomes in the GnomAD database, including 23,380 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 0.55 ( 23380 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

THBS4
NM_003248.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.584

Publications

6 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS4	NM_003248.6 link	c.293-2849G>A		intron_variant	Intron 2 of 21	ENST00000350881.6	NP_003239.2	P35443

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS4	ENST00000350881.6 link	c.293-2849G>A		intron_variant	Intron 2 of 21	1	NM_003248.6	ENSP00000339730.2		P35443

Frequencies

GnomAD3 genomes

AF:

0.549

AC:

83419

AN:

151908

Hom.:

23347

Cov.:

show subpopulations

Gnomad AFR

AF:

0.654

Gnomad AMI

AF:

0.720

Gnomad AMR

AF:

0.528

Gnomad ASJ

AF:

0.560

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.544

Gnomad FIN

AF:

0.494

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.500

Gnomad OTH

AF:

0.545

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.549

AC:

83512

AN:

152022

Hom.:

23380

Cov.:

AF XY:

0.547

AC XY:

40632

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.654

AC:

27141

AN:

41494

American (AMR)

AF:

0.529

AC:

8064

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.560

AC:

1943

AN:

3470

East Asian (EAS)

AF:

0.489

AC:

2528

AN:

5166

South Asian (SAS)

AF:

0.544

AC:

2622

AN:

4820

European-Finnish (FIN)

AF:

0.494

AC:

5207

AN:

10542

Middle Eastern (MID)

AF:

0.627

AC:

183

AN:

292

European-Non Finnish (NFE)

AF:

0.500

AC:

34014

AN:

67960

Other (OTH)

AF:

0.546

AC:

1153

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1902

3803

5705

7606

9508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.520

Hom.:

65216

Bravo

AF:

0.560

Asia WGS

AF:

0.562

AC:

1957

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

3.1

(source)

DANN

Benign

0.64

PhyloP100

0.58

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over