rs2855726

Variant names:

• chr7-74102784-G-A
• rs2855726
• NM_002314.4:c.609-3091G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002314.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMK1	NM_002314.4	MANE Select	c.609-3091G>A		intron	N/A	NP_002305.1	P53667-1
	LIMK1	NM_001204426.2		c.507-3091G>A		intron	N/A	NP_001191355.1	P53667-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMK1	ENST00000336180.7	TSL:1 MANE Select	c.609-3091G>A		intron	N/A	ENSP00000336740.2	P53667-1
	LIMK1	ENST00000435201.5	TSL:1	n.609-3091G>A		intron	N/A	ENSP00000414606.1	P53667-3
	LIMK1	ENST00000483414.1	TSL:1	n.295-3091G>A		intron	N/A

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

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: 89 AN: 292

European-Non Finnish (NFE) AF: 0.321 AC: 21801 AN: 67900

Other (OTH) AF: 0.345 AC: 722 AN: 2094

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.35
DANN	Benign	0.30
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2855726; hg19: chr7-73517114;