15-71284416-A-G

Variant names:

• chr15-71284416-A-G
• rs1442779
• NM_024817.3:c.1015+27701A>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.1015+27701A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 151,494 control chromosomes in the GnomAD database, including 40,864 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 0.73 (40864 hom., cov: 31)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• Publications: 4 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

LOC124903521 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 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.1015+27701A>G		intron	N/A	NP_079093.2
	THSD4	NM_001394532.1		c.1015+27701A>G		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.1015+27701A>G		intron	N/A	ENSP00000261862.8
	THSD4	ENST00000355327.7	TSL:5	c.1015+27701A>G		intron	N/A	ENSP00000347484.3
	ENSG00000297029	ENST00000744765.1		n.207-4636T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.733 AC: 110972 AN: 151374 Hom.: 40821 Cov.: 31

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.733 AC: 111066 AN: 151494 Hom.: 40864 Cov.: 31 AF XY: 0.730 AC XY: 54003 AN XY: 73998

African (AFR) AF: 0.739 AC: 30516 AN: 41268

American (AMR) AF: 0.615 AC: 9375 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2418 AN: 3468

East Asian (EAS) AF: 0.848 AC: 4357 AN: 5140

South Asian (SAS) AF: 0.775 AC: 3726 AN: 4808

European-Finnish (FIN) AF: 0.751 AC: 7886 AN: 10494

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.744 AC: 50433 AN: 67766

Other (OTH) AF: 0.736 AC: 1550 AN: 2106

Alfa AF: 0.747 Hom.: 21180

Bravo AF: 0.725

Asia WGS AF: 0.781 AC: 2714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.9
DANN	Benign	0.71
PhyloP100		0.24
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: rs1442779; hg19: chr15-71576755;