Variant chr15-71215217-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_024817.3(THSD4):c.282C>T(p.Gly94=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0035 in 1,377,654 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 88 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 71 hom. )

Consequence

THSD4
NM_024817.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.220

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]

THSD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 15-71215217-C-T is Benign according to our data. Variant chr15-71215217-C-T is described in ClinVar as [Benign]. Clinvar id is 2691046.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
THSD4	NM_024817.3 linkuse as main transcript	c.282C>T	p.Gly94=	synonymous_variant	4/18	ENST00000261862.8
THSD4	NM_001394532.1 linkuse as main transcript	c.282C>T	p.Gly94=	synonymous_variant	4/18
THSD4	XM_047433080.1 linkuse as main transcript	c.282C>T	p.Gly94=	synonymous_variant	4/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD4	ENST00000261862.8 linkuse as main transcript	c.282C>T	p.Gly94=	synonymous_variant	4/18	5	NM_024817.3	P1	Q6ZMP0-1
THSD4	ENST00000355327.7 linkuse as main transcript	c.282C>T	p.Gly94=	synonymous_variant	4/18	5		P1	Q6ZMP0-1
THSD4	ENST00000620694.1 linkuse as main transcript	c.282C>T	p.Gly94=	synonymous_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.0181

AC:

2746

AN:

151552

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0634

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00613

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000737

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00206

AC:

AN:

31510

Hom.:

AF XY:

0.00136

AC XY:

AN XY:

19118

show subpopulations

Gnomad AFR exome

AF:

0.0895

Gnomad AMR exome

AF:

0.00306

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000287

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.00168

AC:

2062

AN:

1225994

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

834

AN XY:

600374

show subpopulations

Gnomad4 AFR exome

AF:

0.0712

Gnomad4 AMR exome

AF:

0.00441

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000123

Gnomad4 FIN exome

AF:

0.0000332

Gnomad4 NFE exome

AF:

0.0000518

Gnomad4 OTH exome

AF:

0.00413

GnomAD4 genome

AF:

0.0182

AC:

2758

AN:

151660

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

1305

AN XY:

74130

show subpopulations

Gnomad4 AFR

AF:

0.0635

Gnomad4 AMR

AF:

0.00612

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000737

Gnomad4 OTH

AF:

0.0119

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.0214

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 submitter

clinical testing

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Apr 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.6

DANN

Benign

0.82

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.

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