chr13-46155124-C-T

Variant names:

• chr13-46155124-C-T
• rs2296119
• NM_002298.5:c.492-238G>A

Variant summary

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

The NM_002298.5(LCP1):​c.492-238G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,048 control chromosomes in the GnomAD database, including 8,410 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 0.28 (8410 hom., cov: 32)
• Consequence: LCP1 NM_002298.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 6 publications found

Genes affected

LCP1 (HGNC:6528): (lymphocyte cytosolic protein 1) Plastins are a family of actin-binding proteins that are conserved throughout eukaryote evolution and expressed in most tissues of higher eukaryotes. In humans, two ubiquitous plastin isoforms (L and T) have been identified. Plastin 1 (otherwise known as Fimbrin) is a third distinct plastin isoform which is specifically expressed at high levels in the small intestine. The L isoform is expressed only in hemopoietic cell lineages, while the T isoform has been found in all other normal cells of solid tissues that have replicative potential (fibroblasts, endothelial cells, epithelial cells, melanocytes, etc.). However, L-plastin has been found in many types of malignant human cells of non-hemopoietic origin suggesting that its expression is induced accompanying tumorigenesis in solid tissues. [provided by RefSeq, Jul 2008]

CPB2-AS1 (HGNC:39898): (CPB2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP1	NM_002298.5	c.492-238G>A		intron_variant	Intron 5 of 15	ENST00000323076.7	NP_002289.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP1	ENST00000323076.7	c.492-238G>A		intron_variant	Intron 5 of 15	1	NM_002298.5	ENSP00000315757.2
LCP1	ENST00000398576.6	c.492-238G>A		intron_variant	Intron 8 of 18	5		ENSP00000381581.1
LCP1	ENST00000416500.5	c.492-238G>A		intron_variant	Intron 5 of 6	3		ENSP00000408052.1
CPB2-AS1	ENST00000663159.1	n.553-3333C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43198 AN: 151930 Hom.: 8370 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.285 AC: 43302 AN: 152048 Hom.: 8410 Cov.: 32 AF XY: 0.280 AC XY: 20842 AN XY: 74336

African (AFR) AF: 0.546 AC: 22628 AN: 41418

American (AMR) AF: 0.243 AC: 3715 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 668 AN: 3470

East Asian (EAS) AF: 0.287 AC: 1488 AN: 5184

South Asian (SAS) AF: 0.242 AC: 1165 AN: 4824

European-Finnish (FIN) AF: 0.101 AC: 1074 AN: 10588

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11794 AN: 67966

Other (OTH) AF: 0.279 AC: 589 AN: 2112

Alfa AF: 0.212 Hom.: 2687

Bravo AF: 0.308

Asia WGS AF: 0.268 AC: 933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.66
PhyloP100		-0.12
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: rs2296119; hg19: chr13-46729259; COSMIC: COSV59942883; COSMIC: COSV59942883;