chr13-46149459-T-C

Variant names:

• chr13-46149459-T-C
• rs1886040
• NM_002298.5:c.883-1012A>G

Variant summary

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

The NM_002298.5(LCP1):​c.883-1012A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,090 control chromosomes in the GnomAD database, including 26,653 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 0.58 (26653 hom., cov: 32)
• Consequence: LCP1 NM_002298.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 10 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002298.5. 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
	LCP1	NM_002298.5	MANE Select	c.883-1012A>G		intron	N/A	NP_002289.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCP1	ENST00000323076.7	TSL:1 MANE Select	c.883-1012A>G		intron	N/A	ENSP00000315757.2
	LCP1	ENST00000398576.6	TSL:5	c.883-1012A>G		intron	N/A	ENSP00000381581.1
	LCP1	ENST00000469227.5	TSL:3	n.437-1012A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88080 AN: 151972 Hom.: 26602 Cov.: 32

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.580 AC: 88196 AN: 152090 Hom.: 26653 Cov.: 32 AF XY: 0.579 AC XY: 43069 AN XY: 74328

African (AFR) AF: 0.768 AC: 31885 AN: 41494

American (AMR) AF: 0.552 AC: 8436 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1613 AN: 3470

East Asian (EAS) AF: 0.378 AC: 1955 AN: 5168

South Asian (SAS) AF: 0.496 AC: 2389 AN: 4818

European-Finnish (FIN) AF: 0.628 AC: 6635 AN: 10568

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33589 AN: 67978

Other (OTH) AF: 0.518 AC: 1094 AN: 2110

Alfa AF: 0.520 Hom.: 80892

Bravo AF: 0.582

Asia WGS AF: 0.477 AC: 1660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.017
DANN	Benign	0.41
PhyloP100		-1.7
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: rs1886040; hg19: chr13-46723594;