15-71164148-T-C

Variant summary

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

The NM_024817.3(THSD4):c.99+9216T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 141,348 control chromosomes in the GnomAD database, including 7,754 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 0.26 (7754 hom., cov: 27)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549

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]

THSD4-AS1 (HGNC:51420): (THSD4 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD4	NM_024817.3	c.99+9216T>C		intron_variant		ENST00000261862.8
THSD4	NM_001394532.1	c.99+9216T>C		intron_variant
THSD4	XM_047433080.1	c.99+9216T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD4	ENST00000261862.8	c.99+9216T>C		intron_variant		5	NM_024817.3	P1
THSD4-AS1	ENST00000561571.5	n.413+8004A>G		intron_variant, non_coding_transcript_variant		5
THSD4	ENST00000355327.7	c.99+9216T>C		intron_variant		5		P1
THSD4	ENST00000620694.1	c.99+9216T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.257 AC: 36327 AN: 141254 Hom.: 7723 Cov.: 27

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.0783

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0731

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.258 AC: 36401 AN: 141348 Hom.: 7754 Cov.: 27 AF XY: 0.253 AC XY: 17429 AN XY: 68764

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.0731

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.203

Alfa AF: 0.0500 Hom.: 41

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	1.1
Dann	Benign	0.89

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: rs590050; hg19: chr15-71456487;