rs710968

chr7-74083398-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000418310.5(LIMK1):c.145+219A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 151,618 control chromosomes in the GnomAD database, including 44,833 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 0.76 (44833 hom., cov: 28)
• Consequence: LIMK1 ENST00000418310.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIMK1	ENST00000418310.5	c.145+219A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.758 AC: 114771 AN: 151500 Hom.: 44823 Cov.: 28

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.792

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

GnomAD4 genome AF: 0.757 AC: 114807 AN: 151618 Hom.: 44833 Cov.: 28 AF XY: 0.760 AC XY: 56290 AN XY: 74056

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.821

Gnomad4 ASJ AF: 0.876

Gnomad4 EAS AF: 0.865

Gnomad4 SAS AF: 0.838

Gnomad4 FIN AF: 0.856

Gnomad4 NFE AF: 0.837

Gnomad4 OTH AF: 0.794

Alfa AF: 0.792 Hom.: 13879

Bravo AF: 0.746

Asia WGS AF: 0.836 AC: 2908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	3.8
Dann	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs710968; hg19: chr7-73497728;