rs12332694

Variant names:

• chr5-80046166-C-A
• rs12332694
• NM_003248.6:c.292+5886C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003248.6(THBS4):​c.292+5886C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,072 control chromosomes in the GnomAD database, including 6,132 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 0.27 (6132 hom., cov: 32)
• Consequence: THBS4 NM_003248.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS4	NM_003248.6	c.292+5886C>A		intron_variant	Intron 2 of 21	ENST00000350881.6	NP_003239.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS4	ENST00000350881.6	c.292+5886C>A		intron_variant	Intron 2 of 21	1	NM_003248.6	ENSP00000339730.2
THBS4	ENST00000511733.1	c.19+5886C>A		intron_variant	Intron 2 of 21	2		ENSP00000422298.1
THBS4	ENST00000510218.1	n.381+5886C>A		intron_variant	Intron 3 of 3	4
THBS4	ENST00000513310.5	n.350+5886C>A		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41481 AN: 151954 Hom.: 6125 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.273 AC: 41511 AN: 152072 Hom.: 6132 Cov.: 32 AF XY: 0.270 AC XY: 20046 AN XY: 74336

African (AFR) AF: 0.174 AC: 7201 AN: 41484

American (AMR) AF: 0.259 AC: 3956 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1303 AN: 3464

East Asian (EAS) AF: 0.273 AC: 1411 AN: 5172

South Asian (SAS) AF: 0.262 AC: 1264 AN: 4822

European-Finnish (FIN) AF: 0.289 AC: 3049 AN: 10558

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22203 AN: 67966

Other (OTH) AF: 0.282 AC: 595 AN: 2110

Alfa AF: 0.283 Hom.: 1271

Bravo AF: 0.268

Asia WGS AF: 0.260 AC: 907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.9
DANN	Benign	0.73
PhyloP100		-0.049
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs12332694; hg19: chr5-79341989; COSMIC: COSV63467972;