rs1348318

chr15-71168354-A-G

Variant summary

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

The NM_024817.3(THSD4):c.99+13422A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,112 control chromosomes in the GnomAD database, including 25,564 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 0.54 (25564 hom., cov: 33)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD4	NM_024817.3	c.99+13422A>G		intron_variant		ENST00000261862.8
THSD4-AS1	NR_120349.1	n.245-1165T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD4	ENST00000261862.8	c.99+13422A>G		intron_variant		5	NM_024817.3	P1
THSD4-AS1	ENST00000561571.5	n.413+3798T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82389 AN: 151994 Hom.: 25564 Cov.: 33

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.542 AC: 82381 AN: 152112 Hom.: 25564 Cov.: 33 AF XY: 0.545 AC XY: 40528 AN XY: 74350

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.634

Gnomad4 ASJ AF: 0.682

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.569

Alfa AF: 0.658 Hom.: 58857

Bravo AF: 0.525

Asia WGS AF: 0.501 AC: 1738 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	6.0
Dann	Benign	0.68

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: rs1348318; hg19: chr15-71460693;