rs10518942

chr15-71271801-A-Gchr15-71271801-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024817.3(THSD4):c.1015+15086A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,994 control chromosomes in the GnomAD database, including 10,586 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 0.36 (10586 hom., cov: 31)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.558

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]

LOC124903521 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD4	NM_024817.3	c.1015+15086A>G		intron_variant		ENST00000261862.8
LOC124903521	XR_007064701.1	n.955A>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD4	ENST00000261862.8	c.1015+15086A>G		intron_variant		5	NM_024817.3	P1
THSD4	ENST00000355327.7	c.1015+15086A>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54045 AN: 151876 Hom.: 10582 Cov.: 31

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.356 AC: 54054 AN: 151994 Hom.: 10586 Cov.: 31 AF XY: 0.354 AC XY: 26263 AN XY: 74278

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.406

Alfa AF: 0.420 Hom.: 6195

Bravo AF: 0.341

Asia WGS AF: 0.359 AC: 1248 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.4
Dann	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs10518942; hg19: chr15-71564140;