15-71311424-C-T

Position:

• chr15-71311424-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.1015+54709C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 152,186 control chromosomes in the GnomAD database, including 62,806 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 0.90 (62806 hom., cov: 31)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103

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=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD4	NM_024817.3	c.1015+54709C>T		intron_variant		ENST00000261862.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD4	ENST00000261862.8	c.1015+54709C>T		intron_variant		5	NM_024817.3	P1
THSD4	ENST00000355327.7	c.1015+54709C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136635 AN: 152068 Hom.: 62790 Cov.: 31

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.957

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.996

Gnomad FIN AF: 0.986

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.922

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

GnomAD4 genome AF: 0.898 AC: 136691 AN: 152186 Hom.: 62806 Cov.: 31 AF XY: 0.902 AC XY: 67098 AN XY: 74400

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.957

Gnomad4 ASJ AF: 0.983

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.996

Gnomad4 FIN AF: 0.986

Gnomad4 NFE AF: 0.985

Gnomad4 OTH AF: 0.922

Alfa AF: 0.921 Hom.: 11061

Bravo AF: 0.885

Asia WGS AF: 0.977 AC: 3400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.86

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: rs1515677; hg19: chr15-71603763;