NM_003246.4:c.1121-31C>A

Variant names:

• chr15-39587316-C-A
• rs2664141
• NM_003246.4:c.1121-31C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003246.4(THBS1):​c.1121-31C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,048 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: THBS1 NM_003246.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.83
• Publications: 9 publications found

Genes affected

THBS1 (HGNC:11785): (thrombospondin 1) The protein encoded by this gene is a subunit of a disulfide-linked homotrimeric protein. This protein is an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein can bind to fibrinogen, fibronectin, laminin, type V collagen and integrins alpha-V/beta-1. This protein has been shown to play roles in platelet aggregation, angiogenesis, and tumorigenesis. [provided by RefSeq, Jul 2008]

THBS1-IT1 (HGNC:55225): (THBS1 intronic transcript 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003246.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS1	NM_003246.4	MANE Select	c.1121-31C>A		intron	N/A	NP_003237.2
	THBS1-IT1	NR_186398.1		n.*63C>A		downstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THBS1	ENST00000260356.6	TSL:1 MANE Select	c.1121-31C>A		intron	N/A	ENSP00000260356.5
	THBS1	ENST00000466755.1	TSL:2	n.-136C>A		upstream_gene	N/A
	THBS1	ENST00000497720.1	TSL:2	n.-115C>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000420 AC: 1 AN: 238210 AF XY: 0.00000778

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1441048 Hom.: 0 Cov.: 32 AF XY: 0.00000280 AC XY: 2 AN XY: 713806

African (AFR) AF: 0.00 AC: 0 AN: 33278

American (AMR) AF: 0.00 AC: 0 AN: 43948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39384

South Asian (SAS) AF: 0.0000240 AC: 2 AN: 83430

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098976

Other (OTH) AF: 0.00 AC: 0 AN: 59632

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.042
DANN	Benign	0.56
PhyloP100		-2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2664141; hg19: chr15-39879517;