chr5-80079752-T-C

Variant names:

• chr5-80079752-T-C
• rs17885983
• NM_003248.6:c.2512-153T>C

Variant summary

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

The NM_003248.6(THBS4):​c.2512-153T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,188 control chromosomes in the GnomAD database, including 4,937 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 0.23 (4937 hom., cov: 32)
• Consequence: THBS4 NM_003248.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140
• 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]

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS4	NM_003248.6	c.2512-153T>C		intron_variant	Intron 19 of 21	ENST00000350881.6	NP_003239.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS4	ENST00000350881.6	c.2512-153T>C		intron_variant	Intron 19 of 21	1	NM_003248.6	ENSP00000339730.2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34414 AN: 152068 Hom.: 4935 Cov.: 32

Gnomad AFR AF: 0.0696

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.0169

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.226 AC: 34417 AN: 152188 Hom.: 4937 Cov.: 32 AF XY: 0.223 AC XY: 16556 AN XY: 74404

African (AFR) AF: 0.0694 AC: 2884 AN: 41546

American (AMR) AF: 0.195 AC: 2987 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 904 AN: 3470

East Asian (EAS) AF: 0.0170 AC: 88 AN: 5186

South Asian (SAS) AF: 0.235 AC: 1133 AN: 4826

European-Finnish (FIN) AF: 0.295 AC: 3126 AN: 10580

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22614 AN: 67970

Other (OTH) AF: 0.233 AC: 492 AN: 2112

Alfa AF: 0.279 Hom.: 11193

Bravo AF: 0.207

Asia WGS AF: 0.0930 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.36
PhyloP100		0.014
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: rs17885983; hg19: chr5-79375575; COSMIC: COSV63470855; COSMIC: COSV63470855;