12-50195891-CAAAA-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_016357.5(LIMA1):c.973-8_973-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000495 in 1,095,182 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00051 (0 hom.)
• Consequence: LIMA1 NM_016357.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.225

Genes affected

LIMA1 (HGNC:24636): (LIM domain and actin binding 1) This gene encodes a cytoskeleton-associated protein that inhibits actin filament depolymerization and cross-links filaments in bundles. It is downregulated in some cancer cell lines. Alternatively spliced transcript variants encoding different isoforms have been described for this gene, and expression of some of the variants maybe independently regulated. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 12-50195891-CAAAA-C is Benign according to our data. Variant chr12-50195891-CAAAA-C is described in ClinVar as [Likely_benign]. Clinvar id is 3042072.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIMA1	NM_016357.5	c.973-8_973-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000341247.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIMA1	ENST00000341247.9	c.973-8_973-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_016357.5	A2

Frequencies

GnomAD3 genomes AF: 0.0000450 AC: 2 AN: 44468 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000615

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: 0.000522

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000514 AC: 540 AN: 1050714 Hom.: 0 AF XY: 0.000512 AC XY: 264 AN XY: 516026

Gnomad4 AFR exome AF: 0.00455

Gnomad4 AMR exome AF: 0.00119

Gnomad4 ASJ exome AF: 0.000329

Gnomad4 EAS exome AF: 0.000731

Gnomad4 SAS exome AF: 0.000630

Gnomad4 FIN exome AF: 0.000431

Gnomad4 NFE exome AF: 0.000377

Gnomad4 OTH exome AF: 0.000778

GnomAD4 genome AF: 0.0000450 AC: 2 AN: 44468 Hom.: 0 Cov.: 28 AF XY: 0.0000476 AC XY: 1 AN XY: 21004

Gnomad4 AFR AF: 0.0000615

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000522

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

LIMA1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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: rs373254884; hg19: chr12-50589674;