rs2241826

Variant names:

• chr5-80058361-A-G
• rs2241826
• NM_003248.6:c.649+47A>G

Variant summary

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

The NM_003248.6(THBS4):​c.649+47A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,393,678 control chromosomes in the GnomAD database, including 70,061 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 0.30 (7065 hom., cov: 32)
  • Exomes 𝑓: 0.32 (62996 hom.)
• Consequence: THBS4 NM_003248.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470
• Publications: 8 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003248.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS4	NM_003248.6	MANE Select	c.649+47A>G		intron	N/A	NP_003239.2
	THBS4	NM_001306212.2		c.376+47A>G		intron	N/A	NP_001293141.1	E7ES19
	THBS4	NM_001306213.2		c.376+47A>G		intron	N/A	NP_001293142.1	E7ES19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS4	ENST00000350881.6	TSL:1 MANE Select	c.649+47A>G		intron	N/A	ENSP00000339730.2	P35443
	THBS4	ENST00000970348.1		c.696A>G	p.Pro232Pro	synonymous	Exon 4 of 22	ENSP00000640407.1
	THBS4	ENST00000854344.1		c.649+47A>G		intron	N/A	ENSP00000524403.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45736 AN: 152050 Hom.: 7051 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.303

GnomAD2 exomes AF: 0.290 AC: 42698 AN: 147028 AF XY: 0.293

Gnomad AFR exome AF: 0.284

Gnomad AMR exome AF: 0.227

Gnomad ASJ exome AF: 0.363

Gnomad EAS exome AF: 0.279

Gnomad FIN exome AF: 0.288

Gnomad NFE exome AF: 0.320

Gnomad OTH exome AF: 0.315

GnomAD4 exome AF: 0.317 AC: 393704 AN: 1241510 Hom.: 62996 Cov.: 17 AF XY: 0.315 AC XY: 194655 AN XY: 617578

African (AFR) AF: 0.284 AC: 8109 AN: 28544

American (AMR) AF: 0.232 AC: 8148 AN: 35168

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 8677 AN: 24042

East Asian (EAS) AF: 0.286 AC: 9977 AN: 34896

South Asian (SAS) AF: 0.261 AC: 19777 AN: 75826

European-Finnish (FIN) AF: 0.287 AC: 12660 AN: 44088

Middle Eastern (MID) AF: 0.316 AC: 1340 AN: 4246

European-Non Finnish (NFE) AF: 0.327 AC: 308229 AN: 942088

Other (OTH) AF: 0.319 AC: 16787 AN: 52612

GnomAD4 genome AF: 0.301 AC: 45790 AN: 152168 Hom.: 7065 Cov.: 32 AF XY: 0.296 AC XY: 22037 AN XY: 74378

African (AFR) AF: 0.281 AC: 11666 AN: 41528

American (AMR) AF: 0.266 AC: 4068 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1266 AN: 3472

East Asian (EAS) AF: 0.286 AC: 1476 AN: 5166

South Asian (SAS) AF: 0.263 AC: 1270 AN: 4822

European-Finnish (FIN) AF: 0.287 AC: 3039 AN: 10572

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21839 AN: 67988

Other (OTH) AF: 0.301 AC: 637 AN: 2116

Alfa AF: 0.299 Hom.: 2744

Bravo AF: 0.301

Asia WGS AF: 0.277 AC: 968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.49
PhyloP100		-0.47
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2241826;

hg19: chr5-79354184;