13-46149459-T-C

Position:

• chr13-46149459-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCP1	NM_002298.5	c.883-1012A>G		intron_variant		ENST00000323076.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCP1	ENST00000323076.7	c.883-1012A>G		intron_variant		1	NM_002298.5	P1
CPB2-AS1	ENST00000663159.1	n.470-2035T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.768

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.518

Alfa AF: 0.504 Hom.: 33701

Bravo AF: 0.582

Asia WGS AF: 0.477 AC: 1660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.017
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs1886040; hg19: chr13-46723594;