rs7172592

Variant names:

• chr15-71409138-C-A
• rs7172592
• NM_024817.3:c.1016-2549C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-71409138-C-A
• chr15-71409138-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024817.3(THSD4):​c.1016-2549C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000724 in 138,048 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000072 (0 hom., cov: 29)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556
• 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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD4	NM_024817.3	c.1016-2549C>A		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.1016-2549C>A		intron_variant	Intron 6 of 17	5	NM_024817.3	ENSP00000261862.8
THSD4	ENST00000355327.7	c.1016-2549C>A		intron_variant	Intron 6 of 17	5		ENSP00000347484.3

Frequencies

GnomAD3 genomes AF: 0.00000724 AC: 1 AN: 138048 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000783

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000724 AC: 1 AN: 138048 Hom.: 0 Cov.: 29 AF XY: 0.0000151 AC XY: 1 AN XY: 66278

African (AFR) AF: 0.00 AC: 0 AN: 37620

American (AMR) AF: 0.0000783 AC: 1 AN: 12772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3350

East Asian (EAS) AF: 0.00 AC: 0 AN: 3970

South Asian (SAS) AF: 0.00 AC: 0 AN: 4280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64514

Other (OTH) AF: 0.00 AC: 0 AN: 1820

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.49
DANN	Benign	0.34
PhyloP100		-0.56

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: rs7172592; hg19: chr15-71701477;