rs8026019

Positions:

• chr15-71565538-T-A
• chr15-71565538-T-G

Variant summary

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

The NM_024817.3(THSD4):​c.1153-94992T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 152,166 control chromosomes in the GnomAD database, including 55,911 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 0.85 (55911 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176

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]

THSD4 (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 (NFE) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THSD4	NM_024817.3	c.1153-94992T>A		intron_variant		ENST00000261862.8	NP_079093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8	c.1153-94992T>A		intron_variant		5	NM_024817.3	ENSP00000261862.8
THSD4	ENST00000357769.4	c.72+18057T>A		intron_variant		1		ENSP00000350413.4
THSD4	ENST00000355327.7	c.1153-94992T>A		intron_variant		5		ENSP00000347484.3
THSD4	ENST00000567745.5	n.254+18057T>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129672 AN: 152048 Hom.: 55893 Cov.: 32

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.903

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.853 AC: 129737 AN: 152166 Hom.: 55911 Cov.: 32 AF XY: 0.842 AC XY: 62649 AN XY: 74378

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.925

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.842

Gnomad4 NFE AF: 0.907

Gnomad4 OTH AF: 0.848

Alfa AF: 0.887 Hom.: 7447

Bravo AF: 0.851

Asia WGS AF: 0.617 AC: 2147 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	6.7
DANN	Benign	0.84

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: rs8026019; hg19: chr15-71857877;