rs2855726

Positions:

• chr7-74102784-G-A
• chr7-74102784-G-C
• chr7-74102784-G-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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=-0.97).
• 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/exons	MANE	UniProt
LIMK1	NM_002314.4	c.609-3091G>A		intron_variant		ENST00000336180.7
LIMK1	NM_001204426.2	c.507-3091G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIMK1	ENST00000336180.7	c.609-3091G>A		intron_variant		1	NM_002314.4	P1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55083 AN: 151350 Hom.: 10824 Cov.: 29

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.: 29 AF XY: 0.361 AC XY: 26690 AN XY: 73946

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.345

Alfa AF: 0.306 Hom.: 4855

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
DANN	Benign	0.30

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

LitVar

Other links and lift over

dbSNP: rs2855726; hg19: chr7-73517114;