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GeneBe

15-71215118-C-T

Variant summary

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

The NM_024817.3(THSD4):c.183C>T(p.Pro61=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,355,872 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 38 hom., cov: 33)
Exomes 𝑓: 0.0013 ( 35 hom. )

Consequence

THSD4
NM_024817.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.707
Variant links:
Genes affected
THSD4 (HGNC:25835): (thrombospondin type 1 domain containing 4) Predicted to enable hydrolase activity. Predicted to be an extracellular matrix structural constituent. Predicted to act upstream of or within elastic fiber assembly. Located in collagen-containing extracellular matrix and extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.41).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-71215118-C-T is Benign according to our data. Variant chr15-71215118-C-T is described in ClinVar as [Benign]. Clinvar id is 2691042.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=0.707 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 = 0.0137 (2079/151904) while in subpopulation AFR AF= 0.0471 (1955/41510). AF 95% confidence interval is 0.0454. There are 38 homozygotes in gnomad4. There are 957 alleles in male gnomad4 subpopulation. Median coverage is 33. 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 2078 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
THSD4NM_024817.3 linkuse as main transcriptc.183C>T p.Pro61= synonymous_variant 4/18 ENST00000261862.8
THSD4NM_001394532.1 linkuse as main transcriptc.183C>T p.Pro61= synonymous_variant 4/18
THSD4XM_047433080.1 linkuse as main transcriptc.183C>T p.Pro61= synonymous_variant 4/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
THSD4ENST00000261862.8 linkuse as main transcriptc.183C>T p.Pro61= synonymous_variant 4/185 NM_024817.3 P1Q6ZMP0-1
THSD4ENST00000355327.7 linkuse as main transcriptc.183C>T p.Pro61= synonymous_variant 4/185 P1Q6ZMP0-1
THSD4ENST00000620694.1 linkuse as main transcriptc.183C>T p.Pro61= synonymous_variant 4/43

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0137
AC:
2078
AN:
151798
Hom.:
38
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0472
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00585
Gnomad ASJ
AF:
0.000289
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00318
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.0110
GnomAD3 exomes
AF:
0.00144
AC:
65
AN:
45284
Hom.:
2
AF XY:
0.000900
AC XY:
24
AN XY:
26670
show subpopulations
Gnomad AFR exome
AF:
0.0717
Gnomad AMR exome
AF:
0.00194
Gnomad ASJ exome
AF:
0.00201
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000197
Gnomad OTH exome
AF:
0.00241
GnomAD4 exome
AF:
0.00131
AC:
1577
AN:
1203968
Hom.:
35
Cov.:
31
AF XY:
0.00118
AC XY:
695
AN XY:
588136
show subpopulations
Gnomad4 AFR exome
AF:
0.0514
Gnomad4 AMR exome
AF:
0.00349
Gnomad4 ASJ exome
AF:
0.00127
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000100
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000682
Gnomad4 OTH exome
AF:
0.00371
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0137
AC:
2079
AN:
151904
Hom.:
38
Cov.:
33
AF XY:
0.0129
AC XY:
957
AN XY:
74284
show subpopulations
Gnomad4 AFR
AF:
0.0471
Gnomad4 AMR
AF:
0.00584
Gnomad4 ASJ
AF:
0.000289
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.0109
Alfa
AF:
0.0106
Hom.:
0
Bravo
AF:
0.0161
Asia WGS
AF:
0.00350
AC:
12
AN:
3440

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Familial thoracic aortic aneurysm and aortic dissection Benign:1
Benign, criteria provided, single submitterclinical testingCHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern OntarioMay 08, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
Cadd
Benign
14
Dann
Benign
0.95

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: rs150014427; hg19: chr15-71507457; API