rs404375

Positions:

• chr5-80052936-G-A

Variant summary

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

The NM_003248.6(THBS4):​c.293-2849G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,024 control chromosomes in the GnomAD database, including 23,380 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 0.55 (23380 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: THBS4 NM_003248.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.584

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THBS4	NM_003248.6	c.293-2849G>A		intron_variant		ENST00000350881.6	NP_003239.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THBS4	ENST00000350881.6	c.293-2849G>A		intron_variant		1	NM_003248.6	ENSP00000339730.2

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83419 AN: 151908 Hom.: 23347 Cov.: 32

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.545

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.549 AC: 83512 AN: 152022 Hom.: 23380 Cov.: 32 AF XY: 0.547 AC XY: 40632 AN XY: 74298

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.546

Alfa AF: 0.512 Hom.: 40391

Bravo AF: 0.560

Asia WGS AF: 0.562 AC: 1957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.64

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: rs404375; hg19: chr5-79348759; COSMIC: COSV63468411;