rs4777450

chr15-71726130-G-Achr15-71726130-G-C

Variant summary

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

The NM_024817.3(THSD4):c.1358-2419G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,098 control chromosomes in the GnomAD database, including 26,679 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 0.54 (26679 hom., cov: 33)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD4	NM_024817.3	c.1358-2419G>A		intron_variant		ENST00000261862.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD4	ENST00000261862.8	c.1358-2419G>A		intron_variant		5	NM_024817.3	P1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82416 AN: 151980 Hom.: 26679 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.542 AC: 82433 AN: 152098 Hom.: 26679 Cov.: 33 AF XY: 0.549 AC XY: 40813 AN XY: 74346

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.666

Gnomad4 ASJ AF: 0.755

Gnomad4 EAS AF: 0.810

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.560

Alfa AF: 0.635 Hom.: 12461

Bravo AF: 0.526

Asia WGS AF: 0.695 AC: 2419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.34
Dann	Benign	0.45

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: rs4777450; hg19: chr15-72018469;