Genetic Variant TLN1:c.782+237A>G (chr9-35723715-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.46

Publications

16 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLN1	NM_006289.4 link	c.782+237A>G		intron_variant	Intron 7 of 56	ENST00000314888.10	NP_006280.3	Q9Y490

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TLN1	ENST00000314888.10 link	c.782+237A>G	intron_variant	Intron 7 of 56	1	NM_006289.4	ENSP00000316029.9	Q9Y490
TLN1	ENST00000378192.2 link	n.1082A>G	non_coding_transcript_exon_variant	Exon 7 of 7	2
TLN1	ENST00000706939.1 link	c.782+237A>G	intron_variant	Intron 7 of 57			ENSP00000516659.1

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32796

AN:

151822

Hom.:

4345

Cov.:

show subpopulations

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.:

AF XY:

0.262

AC XY:

48533

AN XY:

185086

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

3249

6498

9748

12997

16246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

776

1552

2328

3104

3880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.216

AC:

32768

AN:

151940

Hom.:

4340

Cov.:

AF XY:

0.216

AC XY:

16018

AN XY:

74254

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.283

AC:

19231

AN:

67972

Other (OTH)

AF:

0.219

AC:

463

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1279

2558

3838

5117

6396

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

342

684

1026

1368

1710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.1

(source)

DANN

Benign

0.66

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over