12-50231039-G-A

Variant names:

• chr12-50231039-G-A
• rs7136648
• NM_016357.5:c.165+626C>T

Variant summary

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

The NM_016357.5(LIMA1):​c.165+626C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,084 control chromosomes in the GnomAD database, including 34,700 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 0.66 (34700 hom., cov: 33)
• Consequence: LIMA1 NM_016357.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97
• 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=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMA1	NM_016357.5	MANE Select	c.165+626C>T		intron	N/A	NP_057441.1
	LIMA1	NM_001113546.2		c.165+626C>T		intron	N/A	NP_001107018.1
	LIMA1	NM_001394886.1		c.165+626C>T		intron	N/A	NP_001381815.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMA1	ENST00000341247.9	TSL:1 MANE Select	c.165+626C>T		intron	N/A	ENSP00000340184.4
	LIMA1	ENST00000394943.7	TSL:1	c.165+626C>T		intron	N/A	ENSP00000378400.3
	LIMA1	ENST00000552720.5	TSL:1	n.165+626C>T		intron	N/A	ENSP00000448411.1

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99634 AN: 151968 Hom.: 34650 Cov.: 33

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.656 AC: 99734 AN: 152084 Hom.: 34700 Cov.: 33 AF XY: 0.659 AC XY: 48963 AN XY: 74334

African (AFR) AF: 0.870 AC: 36128 AN: 41510

American (AMR) AF: 0.643 AC: 9831 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1760 AN: 3468

East Asian (EAS) AF: 0.899 AC: 4663 AN: 5186

South Asian (SAS) AF: 0.770 AC: 3718 AN: 4830

European-Finnish (FIN) AF: 0.514 AC: 5412 AN: 10534

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36257 AN: 67962

Other (OTH) AF: 0.639 AC: 1350 AN: 2114

Alfa AF: 0.567 Hom.: 3813

Bravo AF: 0.674

Asia WGS AF: 0.827 AC: 2876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.57
PhyloP100		2.0
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: rs7136648; hg19: chr12-50624822;