rs1913768

chr15-71357205-G-A

Variant summary

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

The NM_024817.3(THSD4):c.1016-54482G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,170 control chromosomes in the GnomAD database, including 1,533 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 0.14 (1533 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD4	NM_024817.3	c.1016-54482G>A		intron_variant		ENST00000261862.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD4	ENST00000261862.8	c.1016-54482G>A		intron_variant		5	NM_024817.3	P1
THSD4	ENST00000355327.7	c.1016-54482G>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21232 AN: 152052 Hom.: 1530 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.140 AC: 21241 AN: 152170 Hom.: 1533 Cov.: 32 AF XY: 0.140 AC XY: 10433 AN XY: 74390

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.132

Alfa AF: 0.153 Hom.: 2402

Bravo AF: 0.131

Asia WGS AF: 0.152 AC: 530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.19
Dann	Benign	0.36

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: rs1913768; hg19: chr15-71649544;