rs7181587

Positions:

• chr15-71494566-C-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+82743C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 151,126 control chromosomes in the GnomAD database, including 4,174 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 0.23 (4174 hom., cov: 29)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.516

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD4	NM_024817.3	c.1152+82743C>T		intron_variant		ENST00000261862.8
LOC107984716	XR_001751787.2	n.616-12893G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD4	ENST00000261862.8	c.1152+82743C>T		intron_variant		5	NM_024817.3	P1
THSD4	ENST00000355327.7	c.1152+82743C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34632 AN: 151008 Hom.: 4174 Cov.: 29

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.0587

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.229 AC: 34658 AN: 151126 Hom.: 4174 Cov.: 29 AF XY: 0.222 AC XY: 16388 AN XY: 73812

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.0586

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.222

Alfa AF: 0.219 Hom.: 4962

Bravo AF: 0.236

Asia WGS AF: 0.112 AC: 391 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	0.63
DANN	Benign	0.66

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: rs7181587; hg19: chr15-71786905;