rs10518948

Variant names:

• chr15-71335630-C-G
• rs10518948
• NM_024817.3:c.1016-76057C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024817.3(THSD4):​c.1016-76057C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0936 in 152,062 control chromosomes in the GnomAD database, including 928 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 0.094 (928 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334
• 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

ENSG00000260586 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD4	NM_024817.3	c.1016-76057C>G		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.1016-76057C>G		intron_variant	Intron 6 of 17	5	NM_024817.3	ENSP00000261862.8
THSD4	ENST00000355327.7	c.1016-76057C>G		intron_variant	Intron 6 of 17	5		ENSP00000347484.3
ENSG00000260586	ENST00000648513.1	n.253+3258C>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0934 AC: 14198 AN: 151944 Hom.: 920 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0508

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.00290

Gnomad SAS AF: 0.0614

Gnomad FIN AF: 0.0472

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0644

Gnomad OTH AF: 0.0876

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

GnomAD4 genome AF: 0.0936 AC: 14239 AN: 152062 Hom.: 928 Cov.: 32 AF XY: 0.0915 AC XY: 6807 AN XY: 74356

African (AFR) AF: 0.190 AC: 7862 AN: 41440

American (AMR) AF: 0.0507 AC: 774 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0513 AC: 178 AN: 3472

East Asian (EAS) AF: 0.00290 AC: 15 AN: 5164

South Asian (SAS) AF: 0.0615 AC: 296 AN: 4814

European-Finnish (FIN) AF: 0.0472 AC: 500 AN: 10588

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0643 AC: 4374 AN: 67990

Other (OTH) AF: 0.0872 AC: 184 AN: 2110

Alfa AF: 0.0767 Hom.: 100

Bravo AF: 0.0995

Asia WGS AF: 0.0530 AC: 184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		-0.33
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: rs10518948; hg19: chr15-71627969;