15-71311424-C-T

Variant names:

• chr15-71311424-C-T
• rs1515677
• NM_024817.3:c.1015+54709C>T

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+54709C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 152,186 control chromosomes in the GnomAD database, including 62,806 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 0.90 (62806 hom., cov: 31)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103
• 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: Franklin by Genoox, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD4	NM_024817.3	MANE Select	c.1015+54709C>T		intron	N/A	NP_079093.2	Q6ZMP0-1
	THSD4	NM_001394532.1		c.1015+54709C>T		intron	N/A	NP_001381461.1	Q6ZMP0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD4	ENST00000261862.8	TSL:5 MANE Select	c.1015+54709C>T		intron	N/A	ENSP00000261862.8	Q6ZMP0-1
	THSD4	ENST00000355327.7	TSL:5	c.1015+54709C>T		intron	N/A	ENSP00000347484.3	Q6ZMP0-1

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136635 AN: 152068 Hom.: 62790 Cov.: 31

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.957

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.996

Gnomad FIN AF: 0.986

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.922

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

GnomAD4 genome AF: 0.898 AC: 136691 AN: 152186 Hom.: 62806 Cov.: 31 AF XY: 0.902 AC XY: 67098 AN XY: 74400

African (AFR) AF: 0.677 AC: 28082 AN: 41466

American (AMR) AF: 0.957 AC: 14642 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.983 AC: 3412 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5155 AN: 5156

South Asian (SAS) AF: 0.996 AC: 4805 AN: 4822

European-Finnish (FIN) AF: 0.986 AC: 10475 AN: 10624

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.985 AC: 66981 AN: 68034

Other (OTH) AF: 0.922 AC: 1950 AN: 2114

Alfa AF: 0.914 Hom.: 11236

Bravo AF: 0.885

Asia WGS AF: 0.977 AC: 3400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.86
PhyloP100		0.10
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: rs1515677; hg19: chr15-71603763;