15-71387620-A-G

Variant summary

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

The NM_024817.3(THSD4):c.1016-24067A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,058 control chromosomes in the GnomAD database, including 28,273 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 (28273 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD4	NM_024817.3	c.1016-24067A>G		intron_variant		ENST00000261862.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD4	ENST00000261862.8	c.1016-24067A>G		intron_variant		5	NM_024817.3	P1
THSD4	ENST00000355327.7	c.1016-24067A>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92430 AN: 151940 Hom.: 28261 Cov.: 32

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.608 AC: 92479 AN: 152058 Hom.: 28273 Cov.: 32 AF XY: 0.606 AC XY: 45052 AN XY: 74326

Gnomad4 AFR AF: 0.616

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.633

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.615

Alfa AF: 0.612 Hom.: 7307

Bravo AF: 0.613

Asia WGS AF: 0.570 AC: 1985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.51
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: rs2044029; hg19: chr15-71679959;