chr9-35723715-T-C

Variant names:

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

Variant summary

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

The NM_006289.4(TLN1):​c.782+237A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 506,174 control chromosomes in the GnomAD database, including 17,665 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 0.22 (4340 hom., cov: 32)
  • Exomes 𝑓: 0.27 (13325 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

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>G		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>G		intron	N/A	ENSP00000316029.9	Q9Y490-1
	TLN1	ENST00000706939.1		c.782+237A>G		intron	N/A	ENSP00000516659.1	Q9Y490-2
	TLN1	ENST00000912154.1		c.782+237A>G		intron	N/A	ENSP00000582213.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32796 AN: 151822 Hom.: 4345 Cov.: 32

Gnomad AFR AF: 0.0614

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.266 AC: 94243 AN: 354234 Hom.: 13325 Cov.: 6 AF XY: 0.262 AC XY: 48533 AN XY: 185086

African (AFR) AF: 0.0538 AC: 497 AN: 9242

American (AMR) AF: 0.282 AC: 2665 AN: 9448

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 2655 AN: 10078

East Asian (EAS) AF: 0.331 AC: 6342 AN: 19176

South Asian (SAS) AF: 0.184 AC: 6085 AN: 33056

European-Finnish (FIN) AF: 0.241 AC: 5145 AN: 21368

Middle Eastern (MID) AF: 0.230 AC: 357 AN: 1552

European-Non Finnish (NFE) AF: 0.284 AC: 65294 AN: 230212

Other (OTH) AF: 0.259 AC: 5203 AN: 20102

GnomAD4 genome AF: 0.216 AC: 32768 AN: 151940 Hom.: 4340 Cov.: 32 AF XY: 0.216 AC XY: 16018 AN XY: 74254

African (AFR) AF: 0.0612 AC: 2536 AN: 41424

American (AMR) AF: 0.283 AC: 4329 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 924 AN: 3466

East Asian (EAS) AF: 0.324 AC: 1672 AN: 5166

South Asian (SAS) AF: 0.186 AC: 893 AN: 4796

European-Finnish (FIN) AF: 0.236 AC: 2487 AN: 10526

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19231 AN: 67972

Other (OTH) AF: 0.219 AC: 463 AN: 2112

Alfa AF: 0.191 Hom.: 1509

Bravo AF: 0.214

Asia WGS AF: 0.218 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.66
PhyloP100		-1.5
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: rs1534847; hg19: chr9-35723712;