rs256447

Variant names:

• chr5-80044128-T-C
• rs256447
• NM_003248.6:c.292+3848T>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.292+3848T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,202 control chromosomes in the GnomAD database, including 4,738 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 0.24 (4738 hom., cov: 32)
• Consequence: THBS4 NM_003248.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS4	NM_003248.6	c.292+3848T>C		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+3848T>C		intron_variant	Intron 2 of 21	1	NM_003248.6	ENSP00000339730.2
THBS4	ENST00000511733.1	c.19+3848T>C		intron_variant	Intron 2 of 21	2		ENSP00000422298.1
THBS4	ENST00000510218.1	n.381+3848T>C		intron_variant	Intron 3 of 3	4
THBS4	ENST00000513310.5	n.350+3848T>C		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36084 AN: 152084 Hom.: 4733 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.237 AC: 36125 AN: 152202 Hom.: 4738 Cov.: 32 AF XY: 0.240 AC XY: 17863 AN XY: 74410

African (AFR) AF: 0.346 AC: 14367 AN: 41522

American (AMR) AF: 0.255 AC: 3902 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 633 AN: 3468

East Asian (EAS) AF: 0.214 AC: 1110 AN: 5176

South Asian (SAS) AF: 0.283 AC: 1365 AN: 4824

European-Finnish (FIN) AF: 0.205 AC: 2175 AN: 10604

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

European-Non Finnish (NFE) AF: 0.173 AC: 11769 AN: 68012

Other (OTH) AF: 0.233 AC: 492 AN: 2108

Alfa AF: 0.222 Hom.: 765

Bravo AF: 0.247

Asia WGS AF: 0.295 AC: 1023 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	1.4
DANN	Benign	0.48
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs256447; hg19: chr5-79339951; COSMIC: COSV63468300;