rs10851839

chr15-71336031-T-Achr15-71336031-T-Cchr15-71336031-T-G

Variant summary

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

The NM_024817.3(THSD4):c.1016-75656T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 152,054 control chromosomes in the GnomAD database, including 29,068 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 0.61 (29068 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD4	NM_024817.3	c.1016-75656T>A		intron_variant		ENST00000261862.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD4	ENST00000261862.8	c.1016-75656T>A		intron_variant		5	NM_024817.3	P1
	ENST00000648513.1	n.253+3659T>A		intron_variant, non_coding_transcript_variant
THSD4	ENST00000355327.7	c.1016-75656T>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92128 AN: 151936 Hom.: 29051 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.606 AC: 92167 AN: 152054 Hom.: 29068 Cov.: 32 AF XY: 0.608 AC XY: 45217 AN XY: 74318

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.724

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.696

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.612

Alfa AF: 0.638 Hom.: 3935

Bravo AF: 0.603

Asia WGS AF: 0.580 AC: 2015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.35
Dann	Benign	0.73

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: rs10851839; hg19: chr15-71628370;