chr5-80066727-G-A

Position:

• chr5-80066727-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000350881.6(THBS4):​c.1195-1246G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 152,320 control chromosomes in the GnomAD database, including 35 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 0.022 (35 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: THBS4 ENST00000350881.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0215 (3281/152320) while in subpopulation SAS AF= 0.0319 (154/4826). AF 95% confidence interval is 0.0278. There are 35 homozygotes in gnomad4. There are 1574 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THBS4	NM_003248.6	c.1195-1246G>A		intron_variant		ENST00000350881.6	NP_003239.2
THBS4-AS1	NR_109930.1	n.2338C>T		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THBS4	ENST00000350881.6	c.1195-1246G>A		intron_variant		1	NM_003248.6	ENSP00000339730	P1
THBS4-AS1	ENST00000503007.5	n.428+1787C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 3273 AN: 152202 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.0246

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0187

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.0265

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.00583

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0215

Gnomad OTH AF: 0.0224

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0215 AC: 3281 AN: 152320 Hom.: 35 Cov.: 32 AF XY: 0.0211 AC XY: 1574 AN XY: 74486

Gnomad4 AFR AF: 0.0247

Gnomad4 AMR AF: 0.0186

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.0264

Gnomad4 SAS AF: 0.0319

Gnomad4 FIN AF: 0.00583

Gnomad4 NFE AF: 0.0215

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0186 Hom.: 9

Bravo AF: 0.0219

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	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs443095; hg19: chr5-79362550;