rs8027305

Positions:

• chr15-71195145-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.100-19890C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0705 in 152,144 control chromosomes in the GnomAD database, including 480 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 0.071 (480 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THSD4	NM_024817.3	c.100-19890C>T		intron_variant		ENST00000261862.8	NP_079093.2
THSD4	NM_001394532.1	c.100-19890C>T		intron_variant			NP_001381461.1
THSD4	XM_047433080.1	c.100-19890C>T		intron_variant			XP_047289036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8	c.100-19890C>T		intron_variant		5	NM_024817.3	ENSP00000261862	P1
THSD4	ENST00000355327.7	c.100-19890C>T		intron_variant		5		ENSP00000347484	P1
THSD4	ENST00000620694.1	c.100-19890C>T		intron_variant		3		ENSP00000484438

Frequencies

GnomAD3 genomes AF: 0.0705 AC: 10725 AN: 152026 Hom.: 481 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0667

Gnomad FIN AF: 0.0461

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0519

Gnomad OTH AF: 0.0559

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

GnomAD4 genome AF: 0.0705 AC: 10732 AN: 152144 Hom.: 480 Cov.: 32 AF XY: 0.0700 AC XY: 5205 AN XY: 74390

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.0372

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0670

Gnomad4 FIN AF: 0.0461

Gnomad4 NFE AF: 0.0519

Gnomad4 OTH AF: 0.0549

Alfa AF: 0.0546 Hom.: 399

Bravo AF: 0.0721

Asia WGS AF: 0.0400 AC: 137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.71
DANN	Benign	0.69

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: rs8027305; hg19: chr15-71487484;