rs3816768

chr15-71748795-C-A

Variant summary

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

The NM_024817.3(THSD4):c.2415+201C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,074 control chromosomes in the GnomAD database, including 6,123 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 0.27 (6123 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD4	NM_024817.3	c.2415+201C>A		intron_variant		ENST00000261862.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD4	ENST00000261862.8	c.2415+201C>A		intron_variant		5	NM_024817.3	P1
THSD4	ENST00000357769.4	c.1335+201C>A		intron_variant		1
THSD4	ENST00000355327.7	c.2415+201C>A		intron_variant		5		P1
THSD4	ENST00000567838.1	n.1338+201C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41552 AN: 151956 Hom.: 6120 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.0819

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.273 AC: 41589 AN: 152074 Hom.: 6123 Cov.: 32 AF XY: 0.272 AC XY: 20214 AN XY: 74352

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.0815

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.272

Alfa AF: 0.254 Hom.: 2265

Bravo AF: 0.265

Asia WGS AF: 0.137 AC: 479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.69
Dann	Benign	0.36

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: rs3816768; hg19: chr15-72041134;