chr15-71565538-T-A

Variant names:

• chr15-71565538-T-A
• rs8026019
• NM_024817.3:c.1153-94992T>A

Variant summary

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

The NM_024817.3(THSD4):​c.1153-94992T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 152,166 control chromosomes in the GnomAD database, including 55,911 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 0.85 (55911 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176
• Publications: 0 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD4	NM_024817.3	c.1153-94992T>A		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.1153-94992T>A		intron_variant	Intron 7 of 17	5	NM_024817.3	ENSP00000261862.8
THSD4	ENST00000357769.4	c.72+18057T>A		intron_variant	Intron 1 of 11	1		ENSP00000350413.4
THSD4	ENST00000355327.7	c.1153-94992T>A		intron_variant	Intron 7 of 17	5		ENSP00000347484.3
THSD4	ENST00000567745.5	n.254+18057T>A		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129672 AN: 152048 Hom.: 55893 Cov.: 32

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.903

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.853 AC: 129737 AN: 152166 Hom.: 55911 Cov.: 32 AF XY: 0.842 AC XY: 62649 AN XY: 74378

African (AFR) AF: 0.852 AC: 35367 AN: 41498

American (AMR) AF: 0.769 AC: 11750 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 3208 AN: 3468

East Asian (EAS) AF: 0.510 AC: 2635 AN: 5164

South Asian (SAS) AF: 0.690 AC: 3330 AN: 4824

European-Finnish (FIN) AF: 0.842 AC: 8913 AN: 10584

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.907 AC: 61674 AN: 68030

Other (OTH) AF: 0.848 AC: 1790 AN: 2112

Alfa AF: 0.887 Hom.: 7447

Bravo AF: 0.851

Asia WGS AF: 0.617 AC: 2147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.7
DANN	Benign	0.84
PhyloP100		-0.18
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: rs8026019; hg19: chr15-71857877;