15-71284416-A-G

Variant summary

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

The NM_024817.3(THSD4):c.1015+27701A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 151,494 control chromosomes in the GnomAD database, including 40,864 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 0.73 (40864 hom., cov: 31)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243

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]

LOC124903521 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD4	NM_024817.3	c.1015+27701A>G		intron_variant		ENST00000261862.8
LOC124903521	XR_007064701.1	n.8293A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD4	ENST00000261862.8	c.1015+27701A>G		intron_variant		5	NM_024817.3	P1
THSD4	ENST00000355327.7	c.1015+27701A>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 110972 AN: 151374 Hom.: 40821 Cov.: 31

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.733 AC: 111066 AN: 151494 Hom.: 40864 Cov.: 31 AF XY: 0.730 AC XY: 54003 AN XY: 73998

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.848

Gnomad4 SAS AF: 0.775

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.736

Alfa AF: 0.742 Hom.: 10213

Bravo AF: 0.725

Asia WGS AF: 0.781 AC: 2714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	3.9
Dann	Benign	0.71

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: rs1442779; hg19: chr15-71576755;