dbSNP rs1885373: TLN1:c.*986G>A (chr9-35696805-C-T) – 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.*986G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 152,260 control chromosomes in the GnomAD database, including 65,589 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 0.92 ( 65581 hom., cov: 32)

Exomes 𝑓: 1.0 ( 8 hom. )

Consequence

TLN1
NM_006289.4 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.67

Publications

7 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=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLN1	NM_006289.4 link	c.*986G>A		downstream_gene_variant		ENST00000314888.10	NP_006280.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLN1	ENST00000314888.10 link	c.*986G>A		downstream_gene_variant		1	NM_006289.4	ENSP00000316029.9
TLN1	ENST00000706939.1 link	c.*986G>A		downstream_gene_variant				ENSP00000516659.1

Frequencies

GnomAD3 genomes

AF:

0.925

AC:

140713

AN:

152126

Hom.:

65535

Cov.:

show subpopulations

Gnomad AFR

AF:

0.799

Gnomad AMI

AF:

0.978

Gnomad AMR

AF:

0.969

Gnomad ASJ

AF:

0.979

Gnomad EAS

AF:

0.899

Gnomad SAS

AF:

0.979

Gnomad FIN

AF:

0.958

Gnomad MID

AF:

0.972

Gnomad NFE

AF:

0.980

Gnomad OTH

AF:

0.949

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Age Distribution

Exome Hom

Variant carriers

<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:

0.925

AC:

140819

AN:

152244

Hom.:

65581

Cov.:

AF XY:

0.926

AC XY:

68925

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.799

AC:

33179

AN:

41508

American (AMR)

AF:

0.969

AC:

14816

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.979

AC:

3398

AN:

3472

East Asian (EAS)

AF:

0.899

AC:

4637

AN:

5158

South Asian (SAS)

AF:

0.978

AC:

4728

AN:

4832

European-Finnish (FIN)

AF:

0.958

AC:

10165

AN:

10614

Middle Eastern (MID)

AF:

0.973

AC:

286

AN:

294

European-Non Finnish (NFE)

AF:

0.980

AC:

66711

AN:

68046

Other (OTH)

AF:

0.949

AC:

2009

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

501

1001

1502

2002

2503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<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:

0.963

Hom.:

91021

Bravo

AF:

0.920

Asia WGS

AF:

0.947

AC:

3296

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.039

(source)

DANN

Benign

0.48

PhyloP100

-1.7

Splicing

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