15-71271801-A-G

Variant names:

• chr15-71271801-A-G
• rs10518942
• NM_024817.3:c.1015+15086A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024817.3(THSD4):​c.1015+15086A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,994 control chromosomes in the GnomAD database, including 10,586 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10586 hom., cov: 31)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.558
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• aortic aneurysm, familial thoracic 12

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Franklin by Genoox

LOC124903521 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD4	NM_024817.3	c.1015+15086A>G		intron_variant	Intron 6 of 17	ENST00000261862.8	NP_079093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8	c.1015+15086A>G		intron_variant	Intron 6 of 17	5	NM_024817.3	ENSP00000261862.8
THSD4	ENST00000355327.7	c.1015+15086A>G		intron_variant	Intron 6 of 17	5		ENSP00000347484.3

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54045 AN: 151876 Hom.: 10582 Cov.: 31

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.400

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.356 AC: 54054 AN: 151994 Hom.: 10586 Cov.: 31 AF XY: 0.354 AC XY: 26263 AN XY: 74278

African (AFR) AF: 0.207 AC: 8567 AN: 41456

American (AMR) AF: 0.314 AC: 4801 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1351 AN: 3470

East Asian (EAS) AF: 0.283 AC: 1460 AN: 5162

South Asian (SAS) AF: 0.442 AC: 2129 AN: 4814

European-Finnish (FIN) AF: 0.388 AC: 4097 AN: 10554

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30184 AN: 67956

Other (OTH) AF: 0.406 AC: 857 AN: 2112

Alfa AF: 0.419 Hom.: 6932

Bravo AF: 0.341

Asia WGS AF: 0.359 AC: 1248 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.71
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10518942; hg19: chr15-71564140;