15-71362463-A-G

Position:

• chr15-71362463-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.1016-49224A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,148 control chromosomes in the GnomAD database, including 3,789 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 0.20 (3789 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THSD4	NM_024817.3	c.1016-49224A>G		intron_variant		ENST00000261862.8	NP_079093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8	c.1016-49224A>G		intron_variant		5	NM_024817.3	ENSP00000261862.8
THSD4	ENST00000355327.7	c.1016-49224A>G		intron_variant		5		ENSP00000347484.3

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29836 AN: 152030 Hom.: 3789 Cov.: 32

Gnomad AFR AF: 0.0715

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.196 AC: 29839 AN: 152148 Hom.: 3789 Cov.: 32 AF XY: 0.201 AC XY: 14974 AN XY: 74368

Gnomad4 AFR AF: 0.0716

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.181

Alfa AF: 0.204 Hom.: 448

Bravo AF: 0.195

Asia WGS AF: 0.322 AC: 1120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.74

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: rs10518954; hg19: chr15-71654802;