rs4777450

Variant names:

• chr15-71726130-G-A
• rs4777450
• NM_024817.3:c.1358-2419G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-71726130-G-A
• chr15-71726130-G-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.1358-2419G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,098 control chromosomes in the GnomAD database, including 26,679 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 0.54 (26679 hom., cov: 33)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD4	NM_024817.3	c.1358-2419G>A		intron_variant	Intron 8 of 17	ENST00000261862.8	NP_079093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8	c.1358-2419G>A		intron_variant	Intron 8 of 17	5	NM_024817.3	ENSP00000261862.8

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82416 AN: 151980 Hom.: 26679 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.542 AC: 82433 AN: 152098 Hom.: 26679 Cov.: 33 AF XY: 0.549 AC XY: 40813 AN XY: 74346

African (AFR) AF: 0.161 AC: 6698 AN: 41512

American (AMR) AF: 0.666 AC: 10180 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2623 AN: 3472

East Asian (EAS) AF: 0.810 AC: 4172 AN: 5152

South Asian (SAS) AF: 0.757 AC: 3645 AN: 4816

European-Finnish (FIN) AF: 0.663 AC: 7012 AN: 10578

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.679 AC: 46158 AN: 67974

Other (OTH) AF: 0.560 AC: 1180 AN: 2108

Alfa AF: 0.633 Hom.: 14230

Bravo AF: 0.526

Asia WGS AF: 0.695 AC: 2419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.34
DANN	Benign	0.45
PhyloP100		-1.2
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: rs4777450; hg19: chr15-72018469;