5-80011929-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001306212.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS4	NM_001306212.2		c.-186+13554C>T		intron	N/A	NP_001293141.1
	THBS4	NM_001306213.2		c.-186+13502C>T		intron	N/A	NP_001293142.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS4	ENST00000510218.1	TSL:4	n.177+13502C>T		intron	N/A
	THBS4	ENST00000513310.5	TSL:4	n.146+13554C>T		intron	N/A

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

African (AFR) AF: 0.185 AC: 7655 AN: 41290

American (AMR) AF: 0.214 AC: 3258 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 576 AN: 3460

East Asian (EAS) AF: 0.184 AC: 945 AN: 5136

South Asian (SAS) AF: 0.253 AC: 1208 AN: 4782

European-Finnish (FIN) AF: 0.194 AC: 2021 AN: 10426

Middle Eastern (MID) AF: 0.154 AC: 45 AN: 292

European-Non Finnish (NFE) AF: 0.147 AC: 9990 AN: 67832

Other (OTH) AF: 0.180 AC: 379 AN: 2106

Alfa AF: 0.157 Hom.: 1433

Bravo AF: 0.178

Asia WGS AF: 0.250 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.6
DANN	Benign	0.76
PhyloP100		-0.27

Splicing

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

Other links and lift over

dbSNP: rs6878264; hg19: chr5-79307752;