12-50195891-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_016357.5(LIMA1):c.973-4G>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (0 hom., cov: 0)
  • Exomes 𝑓: 0.038 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: LIMA1 NM_016357.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00008505
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.101

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 12-50195891-C-A is Benign according to our data. Variant chr12-50195891-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3042369.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome at 4251 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIMA1	NM_016357.5	c.973-4G>T		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.973-4G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_016357.5	A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 5625 AN: 39528 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0681

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.0744

Gnomad MID AF: 0.0244

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.165

GnomAD3 exomes AF: 0.197 AC: 4251 AN: 21594 Hom.: 0 AF XY: 0.210 AC XY: 2422 AN XY: 11558

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.106

Gnomad ASJ exome AF: 0.213

Gnomad EAS exome AF: 0.112

Gnomad SAS exome AF: 0.234

Gnomad FIN exome AF: 0.363

Gnomad NFE exome AF: 0.233

Gnomad OTH exome AF: 0.139

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0381 AC: 39612 AN: 1039840 Hom.: 2 Cov.: 21 AF XY: 0.0373 AC XY: 19036 AN XY: 510760

Gnomad4 AFR exome AF: 0.0267

Gnomad4 AMR exome AF: 0.0395

Gnomad4 ASJ exome AF: 0.0294

Gnomad4 EAS exome AF: 0.0164

Gnomad4 SAS exome AF: 0.0449

Gnomad4 FIN exome AF: 0.0215

Gnomad4 NFE exome AF: 0.0397

Gnomad4 OTH exome AF: 0.0320

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.142 AC: 5623 AN: 39530 Hom.: 0 Cov.: 0 AF XY: 0.129 AC XY: 2439 AN XY: 18970

Gnomad4 AFR AF: 0.0679

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.0744

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.165

Alfa AF: 0.00516 Hom.: 0

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

Jun 03, 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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	3.3
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000085
dbscSNV1_RF	Benign	0.0040
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: rs200957875; hg19: chr12-50589674; COSMIC: COSV57964242; COSMIC: COSV57964242;