ENST00000418310.5:c.-169G>A

Variant names:

• chr7-74082866-G-A
• rs6460071
• ENST00000418310.5:c.-169G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000418310.5(LIMK1):​c.-169G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 549,304 control chromosomes in the GnomAD database, including 9,014 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 0.21 (4932 hom., cov: 32)
  • Exomes 𝑓: 0.13 (4082 hom.)
• Consequence: LIMK1 ENST00000418310.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.813
• Publications: 18 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 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.-169G>A		upstream_gene_variant		5		ENSP00000409717.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31892 AN: 152000 Hom.: 4907 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0781

Gnomad EAS AF: 0.0734

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.129 AC: 51343 AN: 397186 Hom.: 4082 AF XY: 0.127 AC XY: 26542 AN XY: 208204

African (AFR) AF: 0.441 AC: 4920 AN: 11150

American (AMR) AF: 0.107 AC: 1827 AN: 17060

Ashkenazi Jewish (ASJ) AF: 0.0863 AC: 1072 AN: 12418

East Asian (EAS) AF: 0.0852 AC: 2458 AN: 28862

South Asian (SAS) AF: 0.132 AC: 4904 AN: 37154

European-Finnish (FIN) AF: 0.102 AC: 2839 AN: 27704

Middle Eastern (MID) AF: 0.0886 AC: 217 AN: 2448

European-Non Finnish (NFE) AF: 0.126 AC: 29950 AN: 236818

Other (OTH) AF: 0.134 AC: 3156 AN: 23572

GnomAD4 genome AF: 0.210 AC: 31961 AN: 152118 Hom.: 4932 Cov.: 32 AF XY: 0.207 AC XY: 15358 AN XY: 74372

African (AFR) AF: 0.442 AC: 18321 AN: 41440

American (AMR) AF: 0.134 AC: 2046 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0781 AC: 271 AN: 3468

East Asian (EAS) AF: 0.0736 AC: 381 AN: 5176

South Asian (SAS) AF: 0.126 AC: 607 AN: 4828

European-Finnish (FIN) AF: 0.107 AC: 1135 AN: 10594

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8643 AN: 68008

Other (OTH) AF: 0.172 AC: 362 AN: 2110

Alfa AF: 0.164 Hom.: 4446

Bravo AF: 0.220

Asia WGS AF: 0.123 AC: 428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.75
PhyloP100		0.81
PromoterAI		0.011	Neutral

Splicing

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

Other links and lift over

dbSNP: rs6460071; hg19: chr7-73497196;