chr15-71409138-C-T

Position:

• chr15-71409138-C-T

Variant summary

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

The NM_024817.3(THSD4):​c.1016-2549C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 138,090 control chromosomes in the GnomAD database, including 3,163 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 0.22 (3163 hom., cov: 29)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD4	NM_024817.3	c.1016-2549C>T		intron_variant		ENST00000261862.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD4	ENST00000261862.8	c.1016-2549C>T		intron_variant		5	NM_024817.3	P1
THSD4	ENST00000355327.7	c.1016-2549C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 29856 AN: 137986 Hom.: 3145 Cov.: 29

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.217 AC: 29913 AN: 138090 Hom.: 3163 Cov.: 29 AF XY: 0.222 AC XY: 14710 AN XY: 66360

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.203

Alfa AF: 0.193 Hom.: 390

Bravo AF: 0.202

Asia WGS AF: 0.190 AC: 660 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.42

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: rs7172592; hg19: chr15-71701477;