Variant 15-71215226-G-A 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.291G>A(p.Ala97Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,410,700 control chromosomes in the GnomAD database, including 9,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.12 ( 1295 hom., cov: 33)

Exomes 𝑓: 0.11 ( 8701 hom. )

Consequence

THSD4
NM_024817.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.552

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=-0.75).

BP6

Variant 15-71215226-G-A is Benign according to our data. Variant chr15-71215226-G-A is described in ClinVar as [Benign]. Clinvar id is 2691047.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-71215226-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.552 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THSD4	NM_024817.3 linkuse as main transcript	c.291G>A	p.Ala97Ala	synonymous_variant	4/18	ENST00000261862.8	NP_079093.2	Q6ZMP0-1
THSD4	NM_001394532.1 linkuse as main transcript	c.291G>A	p.Ala97Ala	synonymous_variant	4/18		NP_001381461.1
THSD4	XM_047433080.1 linkuse as main transcript	c.291G>A	p.Ala97Ala	synonymous_variant	4/18		XP_047289036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
THSD4	ENST00000261862.8 linkuse as main transcript	c.291G>A	p.Ala97Ala	synonymous_variant	4/18	5	NM_024817.3	ENSP00000261862.8	Q6ZMP0-1
THSD4	ENST00000355327.7 linkuse as main transcript	c.291G>A	p.Ala97Ala	synonymous_variant	4/18	5		ENSP00000347484.3	Q6ZMP0-1
THSD4	ENST00000620694.1 linkuse as main transcript	c.291G>A	p.Ala97Ala	synonymous_variant	4/4	3		ENSP00000484438.1	A0A087X1T0

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18638

AN:

151550

Hom.:

1293

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.0881

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.00444

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.0839

Gnomad MID

AF:

0.159

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.127

GnomAD3 exomes

AF:

0.118

AC:

5085

AN:

42950

Hom.:

352

AF XY:

0.123

AC XY:

3140

AN XY:

25534

show subpopulations

Gnomad AFR exome

AF:

0.228

Gnomad AMR exome

AF:

0.0749

Gnomad ASJ exome

AF:

0.134

Gnomad EAS exome

AF:

0.00361

Gnomad SAS exome

AF:

0.147

Gnomad FIN exome

AF:

0.0980

Gnomad NFE exome

AF:

0.124

Gnomad OTH exome

AF:

0.125

GnomAD4 exome

AF:

0.114

AC:

143265

AN:

1259044

Hom.:

8701

Cov.:

AF XY:

0.114

AC XY:

70645

AN XY:

618206

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.0794

Gnomad4 ASJ exome

AF:

0.129

Gnomad4 EAS exome

AF:

0.00145

Gnomad4 SAS exome

AF:

0.132

Gnomad4 FIN exome

AF:

0.0936

Gnomad4 NFE exome

AF:

0.114

Gnomad4 OTH exome

AF:

0.116

GnomAD4 genome

AF:

0.123

AC:

18658

AN:

151656

Hom.:

1295

Cov.:

AF XY:

0.119

AC XY:

8822

AN XY:

74128

show subpopulations

Gnomad4 AFR

AF:

0.185

Gnomad4 AMR

AF:

0.0880

Gnomad4 ASJ

AF:

0.114

Gnomad4 EAS

AF:

0.00445

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.0839

Gnomad4 NFE

AF:

0.110

Gnomad4 OTH

AF:

0.125

Alfa

AF:

0.120

Hom.:

161

Bravo

AF:

0.127

Asia WGS

AF:

0.0700

AC:

242

AN:

3436

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

Nov 18, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.9

DANN

Benign

0.91

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