NM_024817.3:c.1015+25745G>C

Variant names:

• chr15-71282460-G-C
• rs9806183
• NM_024817.3:c.1015+25745G>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.1015+25745G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 144,962 control chromosomes in the GnomAD database, including 29,465 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 0.64 (29465 hom., cov: 31)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• 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

LOC124903521 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD4	NM_024817.3	c.1015+25745G>C		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.1015+25745G>C		intron_variant	Intron 6 of 17	5	NM_024817.3	ENSP00000261862.8
THSD4	ENST00000355327.7	c.1015+25745G>C		intron_variant	Intron 6 of 17	5		ENSP00000347484.3
ENSG00000297029	ENST00000744765.1	n.207-2680C>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 93293 AN: 144836 Hom.: 29455 Cov.: 31

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.644 AC: 93333 AN: 144962 Hom.: 29465 Cov.: 31 AF XY: 0.645 AC XY: 45496 AN XY: 70590

African (AFR) AF: 0.514 AC: 19545 AN: 38046

American (AMR) AF: 0.594 AC: 8333 AN: 14028

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2031 AN: 3384

East Asian (EAS) AF: 0.850 AC: 4370 AN: 5144

South Asian (SAS) AF: 0.652 AC: 2889 AN: 4432

European-Finnish (FIN) AF: 0.748 AC: 7612 AN: 10178

Middle Eastern (MID) AF: 0.656 AC: 185 AN: 282

European-Non Finnish (NFE) AF: 0.698 AC: 46501 AN: 66582

Other (OTH) AF: 0.650 AC: 1303 AN: 2004

Alfa AF: 0.544 Hom.: 1670

Bravo AF: 0.598

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.43
DANN	Benign	0.45
PhyloP100		-0.13
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: rs9806183; hg19: chr15-71574799;