12-50198709-T-C

Variant names:

• chr12-50198709-T-C
• rs10506291
• NM_016357.5:c.972+2068A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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=-0.77).
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3908 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016357.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMA1	NM_016357.5	MANE Select	c.972+2068A>G		intron	N/A	NP_057441.1	Q9UHB6-1
	LIMA1	NM_001113546.2		c.972+2068A>G		intron	N/A	NP_001107018.1	Q9UHB6-4
	LIMA1	NM_001394886.1		c.972+2068A>G		intron	N/A	NP_001381815.1	Q9UHB6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMA1	ENST00000341247.9	TSL:1 MANE Select	c.972+2068A>G		intron	N/A	ENSP00000340184.4	Q9UHB6-1
	LIMA1	ENST00000394943.7	TSL:1	c.972+2068A>G		intron	N/A	ENSP00000378400.3	Q9UHB6-4
	LIMA1	ENST00000552783.5	TSL:1	c.492+2068A>G		intron	N/A	ENSP00000448779.1	Q9UHB6-5

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

African (AFR) AF: 0.00746 AC: 310 AN: 41556

American (AMR) AF: 0.0136 AC: 208 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0634 AC: 220 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0359 AC: 173 AN: 4824

European-Finnish (FIN) AF: 0.0211 AC: 224 AN: 10614

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0390 AC: 2650 AN: 68026

Other (OTH) AF: 0.0208 AC: 44 AN: 2114

Alfa AF: 0.0346 Hom.: 180

Bravo AF: 0.0236

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism

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: rs10506291; hg19: chr12-50592492;