15-71398952-C-G

Variant names:

• chr15-71398952-C-G
• rs1982234
• NM_024817.3:c.1016-12735C>G

Variant summary

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

The NM_024817.3(THSD4):​c.1016-12735C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,734 control chromosomes in the GnomAD database, including 7,137 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 0.27 (7137 hom., cov: 30)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD4	NM_024817.3	c.1016-12735C>G		intron_variant	Intron 6 of 17	ENST00000261862.8	NP_079093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8	c.1016-12735C>G		intron_variant	Intron 6 of 17	5	NM_024817.3	ENSP00000261862.8
THSD4	ENST00000355327.7	c.1016-12735C>G		intron_variant	Intron 6 of 17	5		ENSP00000347484.3

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41055 AN: 151616 Hom.: 7139 Cov.: 30

Gnomad AFR AF: 0.0642

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.270 AC: 41038 AN: 151734 Hom.: 7137 Cov.: 30 AF XY: 0.268 AC XY: 19887 AN XY: 74086

Gnomad4 AFR AF: 0.0641

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.320

Alfa AF: 0.208 Hom.: 556

Bravo AF: 0.256

Asia WGS AF: 0.196 AC: 685 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	0.57
DANN	Benign	0.76

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: rs1982234; hg19: chr15-71691291;