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GeneBe

15-39581891-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_003246.4(THBS1):c.34C>T(p.Leu12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,614,090 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 33 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 41 hom. )

Consequence

THBS1
NM_003246.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.61
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 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=-0.36).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-39581891-C-T is Benign according to our data. Variant chr15-39581891-C-T is described in ClinVar as [Benign]. Clinvar id is 783705.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=2.61 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0125 (1900/152224) while in subpopulation AFR AF= 0.0438 (1819/41518). AF 95% confidence interval is 0.0421. There are 33 homozygotes in gnomad4. There are 902 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
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 AC in GnomAd at 1893 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
THBS1NM_003246.4 linkuse as main transcriptc.34C>T p.Leu12= synonymous_variant 2/22 ENST00000260356.6
THBS1XM_047432980.1 linkuse as main transcriptc.34C>T p.Leu12= synonymous_variant 2/22
THBS1XM_011521971.3 linkuse as main transcriptc.34C>T p.Leu12= synonymous_variant 2/21

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
THBS1ENST00000260356.6 linkuse as main transcriptc.34C>T p.Leu12= synonymous_variant 2/221 NM_003246.4 P1P07996-1
THBS1ENST00000397591.2 linkuse as main transcriptc.34C>T p.Leu12= synonymous_variant 2/32

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0124
AC:
1893
AN:
152106
Hom.:
33
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0438
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00360
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00717
GnomAD3 exomes
AF:
0.00297
AC:
747
AN:
251358
Hom.:
13
AF XY:
0.00209
AC XY:
284
AN XY:
135844
show subpopulations
Gnomad AFR exome
AF:
0.0414
Gnomad AMR exome
AF:
0.00171
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000880
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.00127
AC:
1860
AN:
1461866
Hom.:
41
Cov.:
31
AF XY:
0.00111
AC XY:
805
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.0447
Gnomad4 AMR exome
AF:
0.00192
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000162
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000594
Gnomad4 OTH exome
AF:
0.00303
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0125
AC:
1900
AN:
152224
Hom.:
33
Cov.:
32
AF XY:
0.0121
AC XY:
902
AN XY:
74416
show subpopulations
Gnomad4 AFR
AF:
0.0438
Gnomad4 AMR
AF:
0.00360
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00710
Alfa
AF:
0.00538
Hom.:
8
Bravo
AF:
0.0138
Asia WGS
AF:
0.00318
AC:
11
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

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 testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
Cadd
Benign
13
Dann
Benign
0.86

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

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

Other links and lift over

dbSNP: rs35248254; hg19: chr15-39874092; API