rs2146880

Positions:

• chr13-46132463-C-A
• chr13-46132463-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002298.5(LCP1):​c.1627-1525G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 151,988 control chromosomes in the GnomAD database, including 14,326 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 0.43 (14326 hom., cov: 31)
• Consequence: LCP1 NM_002298.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCP1	NM_002298.5	c.1627-1525G>T		intron_variant		ENST00000323076.7
LCP1	XM_005266374.3	c.1627-1525G>T		intron_variant
LCP1	XM_047430303.1	c.1627-1525G>T		intron_variant
LCP1	XM_047430304.1	c.1192-1525G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCP1	ENST00000323076.7	c.1627-1525G>T		intron_variant		1	NM_002298.5	P1
CPB2-AS1	ENST00000663159.1	n.470-19031C>A		intron_variant, non_coding_transcript_variant
LCP1	ENST00000398576.6	c.1627-1525G>T		intron_variant		5		P1
LCP1	ENST00000674665.1	c.334-1525G>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65210 AN: 151870 Hom.: 14312 Cov.: 31

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.429 AC: 65268 AN: 151988 Hom.: 14326 Cov.: 31 AF XY: 0.434 AC XY: 32220 AN XY: 74294

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.387

Alfa AF: 0.452 Hom.: 10194

Bravo AF: 0.415

Asia WGS AF: 0.435 AC: 1513 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	1.4
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2146880; hg19: chr13-46706598;