rs7165378

Variant names:

• chr15-71399165-C-T
• rs7165378
• NM_024817.3:c.1016-12522C>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.1016-12522C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 151,900 control chromosomes in the GnomAD database, including 3,243 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 0.20 (3243 hom., cov: 31)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608
• Publications: 3 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024817.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD4	NM_024817.3	MANE Select	c.1016-12522C>T		intron	N/A	NP_079093.2
	THSD4	NM_001394532.1		c.1016-12522C>T		intron	N/A	NP_001381461.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD4	ENST00000261862.8	TSL:5 MANE Select	c.1016-12522C>T		intron	N/A	ENSP00000261862.8
	THSD4	ENST00000355327.7	TSL:5	c.1016-12522C>T		intron	N/A	ENSP00000347484.3

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31074 AN: 151782 Hom.: 3237 Cov.: 31

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.205 AC: 31104 AN: 151900 Hom.: 3243 Cov.: 31 AF XY: 0.205 AC XY: 15220 AN XY: 74232

African (AFR) AF: 0.182 AC: 7530 AN: 41400

American (AMR) AF: 0.155 AC: 2359 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 779 AN: 3470

East Asian (EAS) AF: 0.172 AC: 883 AN: 5146

South Asian (SAS) AF: 0.297 AC: 1425 AN: 4806

European-Finnish (FIN) AF: 0.220 AC: 2320 AN: 10546

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.224 AC: 15201 AN: 67970

Other (OTH) AF: 0.218 AC: 459 AN: 2104

Alfa AF: 0.220 Hom.: 11901

Bravo AF: 0.197

Asia WGS AF: 0.247 AC: 856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.2
DANN	Benign	0.45
PhyloP100		0.61
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: rs7165378; hg19: chr15-71691504;