chr7-74085836-C-T

Variant names:

• chr7-74085836-C-T
• rs1584103497
• NM_002314.4:c.144C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_002314.4(LIMK1):​c.144C>T​(p.Asp48Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000515 in 1,553,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: LIMK1 NM_002314.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.17
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 7-74085836-C-T is Benign according to our data. Variant chr7-74085836-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 719215.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.17 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 7 AD gene.

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.144C>T	p.Asp48Asp	synonymous	Exon 2 of 16	NP_002305.1	P53667-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMK1	ENST00000336180.7	TSL:1 MANE Select	c.144C>T	p.Asp48Asp	synonymous	Exon 2 of 16	ENSP00000336740.2	P53667-1
	LIMK1	ENST00000435201.5	TSL:1	n.144C>T		non_coding_transcript_exon	Exon 2 of 16	ENSP00000414606.1	P53667-3
	LIMK1	ENST00000418310.5	TSL:5	c.234C>T	p.Asp78Asp	synonymous	Exon 2 of 16	ENSP00000409717.1	E9PC47

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000500 AC: 7 AN: 1401202 Hom.: 0 Cov.: 31 AF XY: 0.00000434 AC XY: 3 AN XY: 691642

African (AFR) AF: 0.00 AC: 0 AN: 31900

American (AMR) AF: 0.00 AC: 0 AN: 36368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25230

East Asian (EAS) AF: 0.00 AC: 0 AN: 36118

South Asian (SAS) AF: 0.00 AC: 0 AN: 79510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00000648 AC: 7 AN: 1080874

Other (OTH) AF: 0.00 AC: 0 AN: 58154

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74354

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68050

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.9
DANN	Benign	0.73
PhyloP100		1.2

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: rs1584103497; hg19: chr7-73500166;