rs12425705

Variant names:

• chr12-50216538-T-C
• rs12425705
• NM_016357.5:c.630+5483A>G

Variant summary

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

The NM_016357.5(LIMA1):​c.630+5483A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,974 control chromosomes in the GnomAD database, including 10,220 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 0.36 (10220 hom., cov: 31)
• Consequence: LIMA1 NM_016357.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.735
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIMA1	NM_016357.5	c.630+5483A>G		intron_variant	Intron 4 of 10	ENST00000341247.9	NP_057441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIMA1	ENST00000341247.9	c.630+5483A>G		intron_variant	Intron 4 of 10	1	NM_016357.5	ENSP00000340184.4

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54363 AN: 151856 Hom.: 10223 Cov.: 31

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.368

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.358 AC: 54390 AN: 151974 Hom.: 10220 Cov.: 31 AF XY: 0.352 AC XY: 26166 AN XY: 74300

African (AFR) AF: 0.452 AC: 18715 AN: 41436

American (AMR) AF: 0.269 AC: 4105 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3470

East Asian (EAS) AF: 0.253 AC: 1302 AN: 5152

South Asian (SAS) AF: 0.481 AC: 2319 AN: 4822

European-Finnish (FIN) AF: 0.251 AC: 2646 AN: 10562

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.341 AC: 23172 AN: 67958

Other (OTH) AF: 0.367 AC: 771 AN: 2098

Alfa AF: 0.348 Hom.: 10448

Bravo AF: 0.359

Asia WGS AF: 0.383 AC: 1334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.76
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

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: rs12425705; hg19: chr12-50610321;