rs1348318

Variant names:

• chr15-71168354-A-G
• rs1348318
• NM_024817.3:c.99+13422A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
THSD4	NM_024817.3	c.99+13422A>G		intron_variant	Intron 3 of 17	ENST00000261862.8	NP_079093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8	c.99+13422A>G		intron_variant	Intron 3 of 17	5	NM_024817.3	ENSP00000261862.8

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

African (AFR) AF: 0.218 AC: 9043 AN: 41502

American (AMR) AF: 0.634 AC: 9693 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2368 AN: 3472

East Asian (EAS) AF: 0.517 AC: 2680 AN: 5182

South Asian (SAS) AF: 0.555 AC: 2673 AN: 4818

European-Finnish (FIN) AF: 0.712 AC: 7516 AN: 10552

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.682 AC: 46348 AN: 67990

Other (OTH) AF: 0.569 AC: 1203 AN: 2114

Alfa AF: 0.637 Hom.: 120071

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
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1348318; hg19: chr15-71460693;