Variant 15-71215070-G-GGACGACGGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM2PP5BP3BS2

The NM_024817.3(THSD4):c.137_145dup(p.Asp46_Gly48dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.00000436 in 1,147,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

THSD4
NM_024817.3 inframe_insertion

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.37

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 15-71215070-G-GGACGACGGC is Pathogenic according to our data. Variant chr15-71215070-G-GGACGACGGC is described in ClinVar as [Pathogenic]. Clinvar id is 1675224.Status of the report is no_assertion_criteria_provided, 0 stars.

BP3

Nonframeshift variant in repetitive region in NM_024817.3

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
THSD4	NM_024817.3 linkuse as main transcript	c.137_145dup	p.Asp46_Gly48dup	inframe_insertion	4/18	ENST00000261862.8	NP_079093.2
THSD4	NM_001394532.1 linkuse as main transcript	c.137_145dup	p.Asp46_Gly48dup	inframe_insertion	4/18		NP_001381461.1
THSD4	XM_047433080.1 linkuse as main transcript	c.137_145dup	p.Asp46_Gly48dup	inframe_insertion	4/18		XP_047289036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8 linkuse as main transcript	c.137_145dup	p.Asp46_Gly48dup	inframe_insertion	4/18	5	NM_024817.3	ENSP00000261862	P1	Q6ZMP0-1
THSD4	ENST00000355327.7 linkuse as main transcript	c.137_145dup	p.Asp46_Gly48dup	inframe_insertion	4/18	5		ENSP00000347484	P1	Q6ZMP0-1
THSD4	ENST00000620694.1 linkuse as main transcript	c.137_145dup	p.Asp46_Gly48dup	inframe_insertion	4/4	3		ENSP00000484438

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000436

AC:

AN:

1147886

Hom.:

Cov.:

AF XY:

0.00000724

AC XY:

AN XY:

552680

show subpopulations

Gnomad4 AFR exome

AF:

0.0000436

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000419

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Aortic aneurysm, familial thoracic 12

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over