12-50198709-T-C

Position:

• chr12-50198709-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_016357.5(LIMA1):​c.972+2068A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0257 in 152,298 control chromosomes in the GnomAD database, including 75 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 0.026 (75 hom., cov: 32)
• Consequence: LIMA1 NM_016357.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297

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]

LIMA1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0257 (3908/152298) while in subpopulation NFE AF= 0.039 (2650/68026). AF 95% confidence interval is 0.0377. There are 75 homozygotes in gnomad4. There are 1865 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3908 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIMA1	NM_016357.5	c.972+2068A>G		intron_variant		ENST00000341247.9	NP_057441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIMA1	ENST00000341247.9	c.972+2068A>G		intron_variant		1	NM_016357.5	ENSP00000340184.4

Frequencies

GnomAD3 genomes AF: 0.0257 AC: 3905 AN: 152180 Hom.: 74 Cov.: 32

Gnomad AFR AF: 0.00748

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0352

Gnomad FIN AF: 0.0211

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0390

Gnomad OTH AF: 0.0210

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

GnomAD4 genome AF: 0.0257 AC: 3908 AN: 152298 Hom.: 75 Cov.: 32 AF XY: 0.0250 AC XY: 1865 AN XY: 74460

Gnomad4 AFR AF: 0.00746

Gnomad4 AMR AF: 0.0136

Gnomad4 ASJ AF: 0.0634

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0359

Gnomad4 FIN AF: 0.0211

Gnomad4 NFE AF: 0.0390

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0344 Hom.: 43

Bravo AF: 0.0236

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.77

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: rs10506291; hg19: chr12-50592492;