Genetic Variant LIMK1:c.609-3091G>A (chr7-74102784-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002314.4(LIMK1):c.609-3091G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,456 control chromosomes in the GnomAD database, including 10,871 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 0.36 ( 10871 hom., cov: 29)

Consequence

LIMK1
NM_002314.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.00

Publications

10 publications found

Variant links:

Genes affected

LIMK1 (HGNC:6613): (LIM domain kinase 1) There are approximately 40 known eukaryotic LIM proteins, so named for the LIM domains they contain. LIM domains are highly conserved cysteine-rich structures containing 2 zinc fingers. Although zinc fingers usually function by binding to DNA or RNA, the LIM motif probably mediates protein-protein interactions. LIM kinase-1 and LIM kinase-2 belong to a small subfamily with a unique combination of 2 N-terminal LIM motifs and a C-terminal protein kinase domain. LIMK1 is a serine/threonine kinase that regulates actin polymerization via phosphorylation and inactivation of the actin binding factor cofilin. This protein is ubiquitously expressed during development and plays a role in many cellular processes associated with cytoskeletal structure. This protein also stimulates axon growth and may play a role in brain development. LIMK1 hemizygosity is implicated in the impaired visuospatial constructive cognition of Williams syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Feb 2011]

LIMK1 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=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIMK1	NM_002314.4 link	c.609-3091G>A		intron_variant	Intron 5 of 15	ENST00000336180.7	NP_002305.1	P53667-1
LIMK1	NM_001204426.2 link	c.507-3091G>A		intron_variant	Intron 4 of 14		NP_001191355.1	P53667-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIMK1	ENST00000336180.7 link	c.609-3091G>A		intron_variant	Intron 5 of 15	1	NM_002314.4	ENSP00000336740.2		P53667-1

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55083

AN:

151350

Hom.:

10824

Cov.:

show subpopulations

Gnomad AFR

AF:

0.517

Gnomad AMI

AF:

0.300

Gnomad AMR

AF:

0.302

Gnomad ASJ

AF:

0.287

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.374

Gnomad FIN

AF:

0.251

Gnomad MID

AF:

0.293

Gnomad NFE

AF:

0.321

Gnomad OTH

AF:

0.349

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.364

AC:

55179

AN:

151456

Hom.:

10871

Cov.:

AF XY:

0.361

AC XY:

26690

AN XY:

73946

show subpopulations

African (AFR)

AF:

0.518

AC:

21385

AN:

41310

American (AMR)

AF:

0.302

AC:

4589

AN:

15174

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

995

AN:

3466

East Asian (EAS)

AF:

0.180

AC:

928

AN:

5156

South Asian (SAS)

AF:

0.374

AC:

1798

AN:

4802

European-Finnish (FIN)

AF:

0.251

AC:

2599

AN:

10352

Middle Eastern (MID)

AF:

0.305

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.321

AC:

21801

AN:

67900

Other (OTH)

AF:

0.345

AC:

722

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

1719

3437

5156

6874

8593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.313

Hom.:

8312

Bravo

AF:

0.370

Asia WGS

AF:

0.286

AC:

996

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.35

(source)

DANN

Benign

0.30

PhyloP100

-1.0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over