rs1042

Variant names:

• chr6-169216236-G-A
• rs1042
• NM_003247.5:c.*1586C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-169216236-G-A
• chr6-169216236-G-C

Variant summary

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

The NM_003247.5(THBS2):​c.*1586C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,178 control chromosomes in the GnomAD database, including 1,779 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 0.14 (1779 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: THBS2 NM_003247.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.936
• Publications: 16 publications found

Genes affected

THBS2 (HGNC:11786): (thrombospondin 2) The protein encoded by this gene belongs to the thrombospondin family. It is a disulfide-linked homotrimeric glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein has been shown to function as a potent inhibitor of tumor growth and angiogenesis. Studies of the mouse counterpart suggest that this protein may modulate the cell surface properties of mesenchymal cells and be involved in cell adhesion and migration. [provided by RefSeq, Jul 2008]

THBS2-AS1 (HGNC:56059): (THBS2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THBS2	NM_003247.5	c.*1586C>T		3_prime_UTR_variant	Exon 22 of 22	ENST00000617924.6	NP_003238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THBS2	ENST00000617924.6	c.*1586C>T		3_prime_UTR_variant	Exon 22 of 22	1	NM_003247.5	ENSP00000482784.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21792 AN: 152056 Hom.: 1777 Cov.: 33

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.0807

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.153

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.143 AC: 21821 AN: 152174 Hom.: 1779 Cov.: 33 AF XY: 0.145 AC XY: 10760 AN XY: 74392

African (AFR) AF: 0.145 AC: 6025 AN: 41508

American (AMR) AF: 0.254 AC: 3872 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 444 AN: 3470

East Asian (EAS) AF: 0.133 AC: 688 AN: 5180

South Asian (SAS) AF: 0.209 AC: 1008 AN: 4822

European-Finnish (FIN) AF: 0.0807 AC: 855 AN: 10598

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8547 AN: 68004

Other (OTH) AF: 0.152 AC: 322 AN: 2114

Alfa AF: 0.132 Hom.: 387

Bravo AF: 0.153

Asia WGS AF: 0.167 AC: 578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.7
DANN	Benign	0.74
PhyloP100		0.94
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: rs1042; hg19: chr6-169616331; COSMIC: COSV64677862; COSMIC: COSV64677862;