chr15-71509681-G-C

Variant names:

• chr15-71509681-G-C
• rs4316710
• NM_024817.3:c.1152+97858G>C

Variant summary

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

The NM_024817.3(THSD4):​c.1152+97858G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 152,134 control chromosomes in the GnomAD database, including 49,109 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 0.80 (49109 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314
• 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

LOC107984716 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD4	NM_024817.3	c.1152+97858G>C		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.1152+97858G>C		intron_variant	Intron 7 of 17	5	NM_024817.3	ENSP00000261862.8
THSD4	ENST00000355327.7	c.1152+97858G>C		intron_variant	Intron 7 of 17	5		ENSP00000347484.3

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121915 AN: 152016 Hom.: 49076 Cov.: 32

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.819

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

GnomAD4 genome AF: 0.802 AC: 122006 AN: 152134 Hom.: 49109 Cov.: 32 AF XY: 0.807 AC XY: 60000 AN XY: 74382

African (AFR) AF: 0.754 AC: 31279 AN: 41486

American (AMR) AF: 0.799 AC: 12219 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 2975 AN: 3468

East Asian (EAS) AF: 0.939 AC: 4862 AN: 5176

South Asian (SAS) AF: 0.839 AC: 4043 AN: 4818

European-Finnish (FIN) AF: 0.815 AC: 8623 AN: 10584

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55255 AN: 67994

Other (OTH) AF: 0.821 AC: 1734 AN: 2112

Alfa AF: 0.725 Hom.: 1565

Bravo AF: 0.799

Asia WGS AF: 0.895 AC: 3112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.39
PhyloP100		0.31
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: rs4316710; hg19: chr15-71802020;