rs7181587

Variant names:

• chr15-71494566-C-T
• rs7181587
• NM_024817.3:c.1152+82743C>T

Variant summary

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

The NM_024817.3(THSD4):​c.1152+82743C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 151,126 control chromosomes in the GnomAD database, including 4,174 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 0.23 (4174 hom., cov: 29)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.516
• Publications: 2 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

LOC107984716 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD4	NM_024817.3	c.1152+82743C>T		intron_variant	Intron 7 of 17	ENST00000261862.8	NP_079093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8	c.1152+82743C>T		intron_variant	Intron 7 of 17	5	NM_024817.3	ENSP00000261862.8
THSD4	ENST00000355327.7	c.1152+82743C>T		intron_variant	Intron 7 of 17	5		ENSP00000347484.3

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34632 AN: 151008 Hom.: 4174 Cov.: 29

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.0587

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.229 AC: 34658 AN: 151126 Hom.: 4174 Cov.: 29 AF XY: 0.222 AC XY: 16388 AN XY: 73812

African (AFR) AF: 0.292 AC: 11968 AN: 40984

American (AMR) AF: 0.209 AC: 3169 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 639 AN: 3468

East Asian (EAS) AF: 0.0586 AC: 301 AN: 5136

South Asian (SAS) AF: 0.150 AC: 718 AN: 4774

European-Finnish (FIN) AF: 0.200 AC: 2082 AN: 10422

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15112 AN: 67866

Other (OTH) AF: 0.222 AC: 468 AN: 2110

Alfa AF: 0.221 Hom.: 6287

Bravo AF: 0.236

Asia WGS AF: 0.112 AC: 391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
DANN	Benign	0.66
PhyloP100		-0.52
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: rs7181587; hg19: chr15-71786905;