rs3816768

Variant names:

• chr15-71748795-C-A
• rs3816768
• NM_024817.3:c.2415+201C>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.2415+201C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,074 control chromosomes in the GnomAD database, including 6,123 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 0.27 (6123 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315
• 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

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 (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD4	NM_024817.3	c.2415+201C>A		intron_variant	Intron 14 of 17	ENST00000261862.8	NP_079093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8	c.2415+201C>A		intron_variant	Intron 14 of 17	5	NM_024817.3	ENSP00000261862.8
THSD4	ENST00000357769.4	c.1335+201C>A		intron_variant	Intron 8 of 11	1		ENSP00000350413.4
THSD4	ENST00000355327.7	c.2415+201C>A		intron_variant	Intron 14 of 17	5		ENSP00000347484.3
THSD4	ENST00000567838.1	n.1338+201C>A		intron_variant	Intron 7 of 9	2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41552 AN: 151956 Hom.: 6120 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.0819

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.273 AC: 41589 AN: 152074 Hom.: 6123 Cov.: 32 AF XY: 0.272 AC XY: 20214 AN XY: 74352

African (AFR) AF: 0.357 AC: 14794 AN: 41446

American (AMR) AF: 0.199 AC: 3039 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 642 AN: 3470

East Asian (EAS) AF: 0.0815 AC: 421 AN: 5168

South Asian (SAS) AF: 0.143 AC: 689 AN: 4820

European-Finnish (FIN) AF: 0.327 AC: 3461 AN: 10582

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17682 AN: 67982

Other (OTH) AF: 0.272 AC: 575 AN: 2112

Alfa AF: 0.255 Hom.: 2573

Bravo AF: 0.265

Asia WGS AF: 0.137 AC: 479 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	0.69
DANN	Benign	0.36
PhyloP100		-0.32
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: rs3816768; hg19: chr15-72041134;