5-80011929-C-T

Variant names:

• chr5-80011929-C-T
• rs6878264
• NM_001306212.2:c.-186+13554C>T

Variant summary

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

The NM_001306212.2(THBS4):​c.-186+13554C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 151,452 control chromosomes in the GnomAD database, including 2,363 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 0.17 (2363 hom., cov: 32)
• Consequence: THBS4 NM_001306212.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS4	NM_001306212.2	c.-186+13554C>T		intron_variant	Intron 2 of 22		NP_001293141.1
THBS4	NM_001306213.2	c.-186+13502C>T		intron_variant	Intron 2 of 22		NP_001293142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS4	ENST00000510218.1	n.177+13502C>T		intron_variant	Intron 2 of 3	4
THBS4	ENST00000513310.5	n.146+13554C>T		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26304 AN: 151334 Hom.: 2360 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.174 AC: 26315 AN: 151452 Hom.: 2363 Cov.: 32 AF XY: 0.178 AC XY: 13174 AN XY: 73968

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.180

Alfa AF: 0.158 Hom.: 1088

Bravo AF: 0.178

Asia WGS AF: 0.250 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.6
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6878264; hg19: chr5-79307752;