NM_024817.3:c.1016-2549C>T

Variant names:

• chr15-71409138-C-T
• rs7172592
• NM_024817.3:c.1016-2549C>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.1016-2549C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 138,090 control chromosomes in the GnomAD database, including 3,163 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 0.22 (3163 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: 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.283 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.1016-2549C>T		intron	N/A	NP_079093.2	Q6ZMP0-1
	THSD4	NM_001394532.1		c.1016-2549C>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.1016-2549C>T		intron	N/A	ENSP00000261862.8	Q6ZMP0-1
	THSD4	ENST00000355327.7	TSL:5	c.1016-2549C>T		intron	N/A	ENSP00000347484.3	Q6ZMP0-1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 29856 AN: 137986 Hom.: 3145 Cov.: 29

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.217 AC: 29913 AN: 138090 Hom.: 3163 Cov.: 29 AF XY: 0.222 AC XY: 14710 AN XY: 66360

African (AFR) AF: 0.260 AC: 9802 AN: 37694

American (AMR) AF: 0.291 AC: 3717 AN: 12782

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 444 AN: 3350

East Asian (EAS) AF: 0.137 AC: 543 AN: 3960

South Asian (SAS) AF: 0.238 AC: 1017 AN: 4272

European-Finnish (FIN) AF: 0.252 AC: 2159 AN: 8572

Middle Eastern (MID) AF: 0.222 AC: 60 AN: 270

European-Non Finnish (NFE) AF: 0.180 AC: 11612 AN: 64496

Other (OTH) AF: 0.203 AC: 374 AN: 1838

Alfa AF: 0.193 Hom.: 390

Bravo AF: 0.202

Asia WGS AF: 0.190 AC: 660 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.42
PhyloP100		-0.56
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: rs7172592; hg19: chr15-71701477;