rs12913412

Positions:

• chr15-71469640-G-C
• chr15-71469640-G-T

Variant summary

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

The NM_024817.3(THSD4):​c.1152+57817G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,104 control chromosomes in the GnomAD database, including 2,551 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 0.17 (2551 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THSD4	NM_024817.3	c.1152+57817G>C		intron_variant		ENST00000261862.8	NP_079093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8	c.1152+57817G>C		intron_variant		5	NM_024817.3	ENSP00000261862	P1
THSD4	ENST00000355327.7	c.1152+57817G>C		intron_variant		5		ENSP00000347484	P1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25974 AN: 151986 Hom.: 2555 Cov.: 32

Gnomad AFR AF: 0.0833

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.171 AC: 25989 AN: 152104 Hom.: 2551 Cov.: 32 AF XY: 0.173 AC XY: 12829 AN XY: 74340

Gnomad4 AFR AF: 0.0836

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.180

Alfa AF: 0.0928 Hom.: 142

Bravo AF: 0.168

Asia WGS AF: 0.307 AC: 1067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.088
DANN	Benign	0.56

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: rs12913412; hg19: chr15-71761979;