rs12441227

Positions:

• chr15-71404547-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.1016-7140A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,192 control chromosomes in the GnomAD database, including 1,952 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 0.15 (1952 hom., cov: 33)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THSD4	NM_024817.3	c.1016-7140A>G		intron_variant		ENST00000261862.8	NP_079093.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THSD4	ENST00000261862.8	c.1016-7140A>G		intron_variant		5	NM_024817.3	ENSP00000261862	P1
THSD4	ENST00000355327.7	c.1016-7140A>G		intron_variant		5		ENSP00000347484	P1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22230 AN: 152074 Hom.: 1943 Cov.: 33

Gnomad AFR AF: 0.0562

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.146 AC: 22250 AN: 152192 Hom.: 1952 Cov.: 33 AF XY: 0.150 AC XY: 11139 AN XY: 74398

Gnomad4 AFR AF: 0.0561

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.137

Alfa AF: 0.162 Hom.: 348

Bravo AF: 0.144

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.2
DANN	Benign	0.94

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: rs12441227; hg19: chr15-71696886;