rs2241826

chr5-80058361-A-G

Variant summary

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

The NM_003248.6(THBS4):c.649+47A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,393,678 control chromosomes in the GnomAD database, including 70,061 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 0.30 (7065 hom., cov: 32)
  • Exomes 𝑓: 0.32 (62996 hom.)
• Consequence: THBS4 NM_003248.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470

Genes affected

THBS4 (HGNC:11788): (thrombospondin 4) The protein encoded by this gene belongs to the thrombospondin protein family. Thrombospondin family members are adhesive glycoproteins that mediate cell-to-cell and cell-to-matrix interactions. This protein forms a pentamer and can bind to heparin and calcium. It is involved in local signaling in the developing and adult nervous system, and it contributes to spinal sensitization and neuropathic pain states. This gene is activated during the stromal response to invasive breast cancer. It may also play a role in inflammatory responses in Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

THBS4-AS1 (HGNC:40583): (THBS4 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THBS4	NM_003248.6	c.649+47A>G		intron_variant		ENST00000350881.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THBS4	ENST00000350881.6	c.649+47A>G		intron_variant		1	NM_003248.6	P1
THBS4-AS1	ENST00000503007.5	n.429-5460T>C		intron_variant, non_coding_transcript_variant		3
THBS4	ENST00000511733.1	c.376+47A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45736 AN: 152050 Hom.: 7051 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.303

GnomAD3 exomes AF: 0.290 AC: 42698 AN: 147028 Hom.: 6262 AF XY: 0.293 AC XY: 22773 AN XY: 77790

Gnomad AFR exome AF: 0.284

Gnomad AMR exome AF: 0.227

Gnomad ASJ exome AF: 0.363

Gnomad EAS exome AF: 0.279

Gnomad SAS exome AF: 0.263

Gnomad FIN exome AF: 0.288

Gnomad NFE exome AF: 0.320

Gnomad OTH exome AF: 0.315

GnomAD4 exome AF: 0.317 AC: 393704 AN: 1241510 Hom.: 62996 Cov.: 17 AF XY: 0.315 AC XY: 194655 AN XY: 617578

Gnomad4 AFR exome AF: 0.284

Gnomad4 AMR exome AF: 0.232

Gnomad4 ASJ exome AF: 0.361

Gnomad4 EAS exome AF: 0.286

Gnomad4 SAS exome AF: 0.261

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.319

GnomAD4 genome AF: 0.301 AC: 45790 AN: 152168 Hom.: 7065 Cov.: 32 AF XY: 0.296 AC XY: 22037 AN XY: 74378

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.301

Alfa AF: 0.300 Hom.: 1769

Bravo AF: 0.301

Asia WGS AF: 0.277 AC: 968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.6
Dann	Benign	0.49

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: rs2241826; hg19: chr5-79354184;