NM_024817.3:c.1016-24067A>G

Variant names:

• chr15-71387620-A-G
• rs2044029
• NM_024817.3:c.1016-24067A>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.1016-24067A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,058 control chromosomes in the GnomAD database, including 28,273 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 0.61 (28273 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 11 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD4	NM_024817.3	c.1016-24067A>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.1016-24067A>G		intron_variant	Intron 6 of 17	5	NM_024817.3	ENSP00000261862.8
THSD4	ENST00000355327.7	c.1016-24067A>G		intron_variant	Intron 6 of 17	5		ENSP00000347484.3

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92430 AN: 151940 Hom.: 28261 Cov.: 32

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.608 AC: 92479 AN: 152058 Hom.: 28273 Cov.: 32 AF XY: 0.606 AC XY: 45052 AN XY: 74326

African (AFR) AF: 0.616 AC: 25538 AN: 41478

American (AMR) AF: 0.596 AC: 9114 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2195 AN: 3468

East Asian (EAS) AF: 0.717 AC: 3699 AN: 5162

South Asian (SAS) AF: 0.505 AC: 2427 AN: 4810

European-Finnish (FIN) AF: 0.572 AC: 6044 AN: 10564

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.608 AC: 41336 AN: 67982

Other (OTH) AF: 0.615 AC: 1296 AN: 2108

Alfa AF: 0.610 Hom.: 44749

Bravo AF: 0.613

Asia WGS AF: 0.570 AC: 1985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.51
DANN	Benign	0.71
PhyloP100		-1.3
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: rs2044029; hg19: chr15-71679959;