rs1534847

Variant names:

• chr9-35723715-T-A
• rs1534847
• NM_006289.4:c.782+237A>T

Your query was ambiguous. Multiple possible variants found:

• chr9-35723715-T-A
• chr9-35723715-T-C

Variant summary

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

The NM_006289.4(TLN1):​c.782+237A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TLN1 NM_006289.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 16 publications found

Genes affected

TLN1 (HGNC:11845): (talin 1) This gene encodes a cytoskeletal protein that is concentrated in areas of cell-substratum and cell-cell contacts. The encoded protein plays a significant role in the assembly of actin filaments and in spreading and migration of various cell types, including fibroblasts and osteoclasts. It codistributes with integrins in the cell surface membrane in order to assist in the attachment of adherent cells to extracellular matrices and of lymphocytes to other cells. The N-terminus of this protein contains elements for localization to cell-extracellular matrix junctions. The C-terminus contains binding sites for proteins such as beta-1-integrin, actin, and vinculin. [provided by RefSeq, Feb 2009]

TLN1 Gene-Disease associations (from GenCC):

• idiopathic spontaneous coronary artery dissection

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia
• thrombocytopenia

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

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=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006289.4. 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
	TLN1	NM_006289.4	MANE Select	c.782+237A>T		intron	N/A	NP_006280.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLN1	ENST00000314888.10	TSL:1 MANE Select	c.782+237A>T		intron	N/A	ENSP00000316029.9	Q9Y490-1
	TLN1	ENST00000706939.1		c.782+237A>T		intron	N/A	ENSP00000516659.1	Q9Y490-2
	TLN1	ENST00000912154.1		c.782+237A>T		intron	N/A	ENSP00000582213.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 355258 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 185602

African (AFR) AF: 0.00 AC: 0 AN: 9242

American (AMR) AF: 0.00 AC: 0 AN: 9470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10118

East Asian (EAS) AF: 0.00 AC: 0 AN: 19258

South Asian (SAS) AF: 0.00 AC: 0 AN: 33104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1554

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 230930

Other (OTH) AF: 0.00 AC: 0 AN: 20160

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1509

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.91
DANN	Benign	0.74
PhyloP100		-1.5

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: rs1534847; hg19: chr9-35723712;