chr12-50176344-A-G

Position:

• chr12-50176344-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016357.5(LIMA1):​c.*720T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,124 control chromosomes in the GnomAD database, including 7,168 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 0.29 (7167 hom., cov: 32)
  • Exomes 𝑓: 0.21 (1 hom.)
• Consequence: LIMA1 NM_016357.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.771

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIMA1	NM_016357.5	c.*720T>C		3_prime_UTR_variant	11/11	ENST00000341247.9	NP_057441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIMA1	ENST00000341247	c.*720T>C		3_prime_UTR_variant	11/11	1	NM_016357.5	ENSP00000340184.4

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44725 AN: 151992 Hom.: 7173 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.214 AC: 3 AN: 14 Hom.: 1 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 FIN exome AF: 0.0833

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.294 AC: 44716 AN: 152110 Hom.: 7167 Cov.: 32 AF XY: 0.286 AC XY: 21240 AN XY: 74358

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.288

Alfa AF: 0.337 Hom.: 8502

Bravo AF: 0.283

Asia WGS AF: 0.205 AC: 715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.65

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: rs3184122; hg19: chr12-50570127; COSMIC: COSV57968869; COSMIC: COSV57968869;