rs11635579

chr15-71498009-A-Cchr15-71498009-A-Gchr15-71498009-A-T

Variant summary

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

The NM_024817.3(THSD4):c.1152+86186A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,102 control chromosomes in the GnomAD database, including 16,781 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 0.43 (16781 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547

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]

LOC107984716 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD4	NM_024817.3	c.1152+86186A>C		intron_variant		ENST00000261862.8
LOC107984716	XR_001751787.2	n.616-16336T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD4	ENST00000261862.8	c.1152+86186A>C		intron_variant		5	NM_024817.3	P1
THSD4	ENST00000355327.7	c.1152+86186A>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64981 AN: 151984 Hom.: 16774 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.427 AC: 64993 AN: 152102 Hom.: 16781 Cov.: 32 AF XY: 0.436 AC XY: 32375 AN XY: 74338

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.462

Alfa AF: 0.505 Hom.: 32669

Bravo AF: 0.418

Asia WGS AF: 0.654 AC: 2275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.4
Dann	Benign	0.72

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: rs11635579; hg19: chr15-71790348;