rs8027305

Variant names:

• chr15-71195145-C-T
• rs8027305
• NM_024817.3:c.100-19890C>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.100-19890C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0705 in 152,144 control chromosomes in the GnomAD database, including 480 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 0.071 (480 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• 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

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 (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD4	NM_024817.3	c.100-19890C>T		intron_variant	Intron 3 of 17	ENST00000261862.8	NP_079093.2
THSD4	NM_001394532.1	c.100-19890C>T		intron_variant	Intron 3 of 17		NP_001381461.1
THSD4	XM_047433080.1	c.100-19890C>T		intron_variant	Intron 3 of 17		XP_047289036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8	c.100-19890C>T		intron_variant	Intron 3 of 17	5	NM_024817.3	ENSP00000261862.8
THSD4	ENST00000355327.7	c.100-19890C>T		intron_variant	Intron 3 of 17	5		ENSP00000347484.3
THSD4	ENST00000620694.1	c.100-19890C>T		intron_variant	Intron 3 of 3	3		ENSP00000484438.1

Frequencies

GnomAD3 genomes AF: 0.0705 AC: 10725 AN: 152026 Hom.: 481 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0667

Gnomad FIN AF: 0.0461

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0519

Gnomad OTH AF: 0.0559

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

GnomAD4 genome AF: 0.0705 AC: 10732 AN: 152144 Hom.: 480 Cov.: 32 AF XY: 0.0700 AC XY: 5205 AN XY: 74390

African (AFR) AF: 0.132 AC: 5464 AN: 41486

American (AMR) AF: 0.0372 AC: 569 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0670 AC: 322 AN: 4808

European-Finnish (FIN) AF: 0.0461 AC: 489 AN: 10604

Middle Eastern (MID) AF: 0.0308 AC: 9 AN: 292

European-Non Finnish (NFE) AF: 0.0519 AC: 3528 AN: 67990

Other (OTH) AF: 0.0549 AC: 116 AN: 2114

Alfa AF: 0.0557 Hom.: 847

Bravo AF: 0.0721

Asia WGS AF: 0.0400 AC: 137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.71
DANN	Benign	0.69
PhyloP100		-1.4
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: rs8027305; hg19: chr15-71487484;