rs12912888

chr15-71564345-G-Achr15-71564345-G-C

Variant summary

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

The NM_024817.3(THSD4):c.1153-96185G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 152,144 control chromosomes in the GnomAD database, including 53,240 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 0.83 (53240 hom., cov: 32)
• Consequence: THSD4 NM_024817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THSD4	NM_024817.3	c.1153-96185G>A		intron_variant		ENST00000261862.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THSD4	ENST00000261862.8	c.1153-96185G>A		intron_variant		5	NM_024817.3	P1
THSD4	ENST00000357769.4	c.72+16864G>A		intron_variant		1
THSD4	ENST00000355327.7	c.1153-96185G>A		intron_variant		5		P1
THSD4	ENST00000567745.5	n.254+16864G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126622 AN: 152026 Hom.: 53222 Cov.: 32

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.838

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

GnomAD4 genome AF: 0.833 AC: 126687 AN: 152144 Hom.: 53240 Cov.: 32 AF XY: 0.823 AC XY: 61212 AN XY: 74362

Gnomad4 AFR AF: 0.846

Gnomad4 AMR AF: 0.761

Gnomad4 ASJ AF: 0.909

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.809

Gnomad4 NFE AF: 0.875

Gnomad4 OTH AF: 0.836

Alfa AF: 0.843 Hom.: 8107

Bravo AF: 0.833

Asia WGS AF: 0.613 AC: 2134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	2.4
Dann	Benign	0.34

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: rs12912888; hg19: chr15-71856684;