rs385771

Variant names:

• chr5-80024854-T-C
• rs385771
• NM_001306212.2:c.-185-15223T>C

Variant summary

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

The NM_001306212.2(THBS4):​c.-185-15223T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,106 control chromosomes in the GnomAD database, including 4,536 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 (4536 hom., cov: 32)
• Consequence: THBS4 NM_001306212.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS4	NM_001306212.2	c.-185-15223T>C		intron_variant	Intron 2 of 22		NP_001293141.1
THBS4	NM_001306213.2	c.-185-15223T>C		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.178-15223T>C		intron_variant	Intron 2 of 3	4
THBS4	ENST00000513310.5	n.147-15223T>C		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35379 AN: 151986 Hom.: 4522 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.233 AC: 35429 AN: 152106 Hom.: 4536 Cov.: 32 AF XY: 0.236 AC XY: 17542 AN XY: 74368

African (AFR) AF: 0.335 AC: 13899 AN: 41470

American (AMR) AF: 0.247 AC: 3772 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 660 AN: 3468

East Asian (EAS) AF: 0.202 AC: 1045 AN: 5174

South Asian (SAS) AF: 0.292 AC: 1409 AN: 4824

European-Finnish (FIN) AF: 0.202 AC: 2138 AN: 10584

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11703 AN: 67990

Other (OTH) AF: 0.234 AC: 493 AN: 2110

Alfa AF: 0.199 Hom.: 1805

Bravo AF: 0.242

Asia WGS AF: 0.304 AC: 1056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.77
PhyloP100		-0.27

Splicing

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

Other links and lift over

dbSNP: rs385771; hg19: chr5-79320677; COSMIC: COSV72512247;