rs710968

Variant names:

• chr7-74083398-A-G
• rs710968
• ENST00000418310.5:c.145+219A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIMK1	ENST00000418310.5	c.145+219A>G		intron_variant	Intron 1 of 15	5		ENSP00000409717.1

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

African (AFR) AF: 0.541 AC: 22331 AN: 41312

American (AMR) AF: 0.821 AC: 12530 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3037 AN: 3466

East Asian (EAS) AF: 0.865 AC: 4356 AN: 5038

South Asian (SAS) AF: 0.838 AC: 4017 AN: 4794

European-Finnish (FIN) AF: 0.856 AC: 9047 AN: 10572

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.837 AC: 56841 AN: 67870

Other (OTH) AF: 0.794 AC: 1668 AN: 2100

Alfa AF: 0.745 Hom.: 19690

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
PhyloP100		-2.6
PromoterAI		0.022	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs710968; hg19: chr7-73497728;