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5-80055915-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003248.6(THBS4):c.423A>G(p.Leu141=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,614,124 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 Benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00077 ( 1 hom. )

Consequence

THBS4
NM_003248.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.126
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-AS1 (HGNC:40583): (THBS4 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-80055915-A-G is Benign according to our data. Variant chr5-80055915-A-G is described in ClinVar as [Benign]. Clinvar id is 783438.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.126 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
THBS4NM_003248.6 linkuse as main transcriptc.423A>G p.Leu141= synonymous_variant 3/22 ENST00000350881.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
THBS4ENST00000350881.6 linkuse as main transcriptc.423A>G p.Leu141= synonymous_variant 3/221 NM_003248.6 P1
THBS4-AS1ENST00000503007.5 linkuse as main transcriptn.429-3014T>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00355
AC:
541
AN:
152188
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0104
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00367
Gnomad ASJ
AF:
0.000864
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000544
Gnomad OTH
AF:
0.00718
GnomAD3 exomes
AF:
0.00135
AC:
339
AN:
251484
Hom.:
2
AF XY:
0.00102
AC XY:
139
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.0102
Gnomad AMR exome
AF:
0.00280
Gnomad ASJ exome
AF:
0.000595
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000475
Gnomad OTH exome
AF:
0.00261
GnomAD4 exome
AF:
0.000774
AC:
1132
AN:
1461818
Hom.:
1
Cov.:
37
AF XY:
0.000666
AC XY:
484
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.0104
Gnomad4 AMR exome
AF:
0.00295
Gnomad4 ASJ exome
AF:
0.000842
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000468
Gnomad4 OTH exome
AF:
0.00159
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00356
AC:
542
AN:
152306
Hom.:
3
Cov.:
33
AF XY:
0.00356
AC XY:
265
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.0103
Gnomad4 AMR
AF:
0.00366
Gnomad4 ASJ
AF:
0.000864
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000544
Gnomad4 OTH
AF:
0.00710
Alfa
AF:
0.00135
Hom.:
0
Bravo
AF:
0.00453
EpiCase
AF:
0.000600
EpiControl
AF:
0.000533

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 submitterclinical testingInvitaeMar 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
Cadd
Benign
0.66
Dann
Benign
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs17882513; hg19: chr5-79351738; API