15-71131670-T-C

Variant names:

• chr15-71131670-T-C
• rs12904863
• NM_024817.3:c.-79-9779T>C

Variant summary

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

The NM_024817.3(THSD4):​c.-79-9779T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,174 control chromosomes in the GnomAD database, including 1,145 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 0.10 (1145 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.995

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD4	NM_024817.3	c.-79-9779T>C		intron_variant	Intron 1 of 17	ENST00000261862.8	NP_079093.2
THSD4	NM_001394532.1	c.-79-9779T>C		intron_variant	Intron 1 of 17		NP_001381461.1
THSD4	XM_047433080.1	c.-80+1133T>C		intron_variant	Intron 1 of 17		XP_047289036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8	c.-79-9779T>C		intron_variant	Intron 1 of 17	5	NM_024817.3	ENSP00000261862.8
THSD4	ENST00000355327.7	c.-79-9779T>C		intron_variant	Intron 1 of 17	5		ENSP00000347484.3
THSD4	ENST00000620694.1	c.-79-9779T>C		intron_variant	Intron 1 of 3	3		ENSP00000484438.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15762 AN: 152058 Hom.: 1142 Cov.: 32

Gnomad AFR AF: 0.0767

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0653

Gnomad ASJ AF: 0.0571

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0971

Gnomad OTH AF: 0.0893

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

GnomAD4 genome AF: 0.104 AC: 15784 AN: 152174 Hom.: 1145 Cov.: 32 AF XY: 0.107 AC XY: 7971 AN XY: 74404

Gnomad4 AFR AF: 0.0769

Gnomad4 AMR AF: 0.0652

Gnomad4 ASJ AF: 0.0571

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.0971

Gnomad4 OTH AF: 0.0950

Alfa AF: 0.0935 Hom.: 190

Bravo AF: 0.0972

Asia WGS AF: 0.288 AC: 1001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.7
DANN	Benign	0.78

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: rs12904863; hg19: chr15-71424009;