1-155202588-A-G

Variant names:

• chr1-155202588-A-G
• rs2066981
• NM_007112.5:c.958-187T>C

Variant summary

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

The NM_007112.5(THBS3):​c.958-187T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,788 control chromosomes in the GnomAD database, including 13,469 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 0.42 (13469 hom., cov: 31)
• Consequence: THBS3 NM_007112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 33 publications found

Genes affected

THBS3 (HGNC:11787): (thrombospondin 3) The protein encoded by this gene belongs to the thrombospondin family. Thrombospondin family members are adhesive glycoproteins that mediate cell-to-cell and cell-to-matrix interactions. This protein forms a pentameric molecule linked by a single disulfide bond. This gene shares a common promoter with metaxin 1. Alternate splicing results in coding and non-coding transcript variants. [provided by RefSeq, Nov 2011]

THBS3-AS1 (HGNC:40582): (THBS3 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007112.5. 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
	THBS3	NM_007112.5	MANE Select	c.958-187T>C		intron	N/A	NP_009043.1	P49746-1
	THBS3	NM_001407490.1		c.1129-187T>C		intron	N/A	NP_001394419.1
	THBS3	NM_001407487.1		c.958-187T>C		intron	N/A	NP_001394416.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS3	ENST00000368378.7	TSL:1 MANE Select	c.958-187T>C		intron	N/A	ENSP00000357362.3	P49746-1
	THBS3	ENST00000541576.5	TSL:1	c.931-187T>C		intron	N/A	ENSP00000444792.2	F5H4Z8
	THBS3	ENST00000541990.5	TSL:1	c.-536-187T>C		intron	N/A	ENSP00000437353.1	Q2HIZ1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63212 AN: 151670 Hom.: 13455 Cov.: 31

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.417 AC: 63262 AN: 151788 Hom.: 13469 Cov.: 31 AF XY: 0.417 AC XY: 30898 AN XY: 74150

African (AFR) AF: 0.344 AC: 14250 AN: 41366

American (AMR) AF: 0.364 AC: 5559 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1701 AN: 3464

East Asian (EAS) AF: 0.210 AC: 1086 AN: 5164

South Asian (SAS) AF: 0.458 AC: 2207 AN: 4818

European-Finnish (FIN) AF: 0.443 AC: 4662 AN: 10522

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32182 AN: 67868

Other (OTH) AF: 0.426 AC: 898 AN: 2108

Alfa AF: 0.465 Hom.: 17420

Bravo AF: 0.401

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.21
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs2066981; hg19: chr1-155172379;