rs2296119

Positions:

• chr13-46155124-C-T

Variant summary

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

The ENST00000323076.7(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 ENST00000323076.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121

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 (AFR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCP1	NM_002298.5	c.492-238G>A		intron_variant		ENST00000323076.7	NP_002289.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCP1	ENST00000323076.7	c.492-238G>A		intron_variant		1	NM_002298.5	ENSP00000315757	P1
CPB2-AS1	ENST00000663159.1	n.553-3333C>T		intron_variant, non_coding_transcript_variant
LCP1	ENST00000398576.6	c.492-238G>A		intron_variant		5		ENSP00000381581	P1
LCP1	ENST00000416500.5	c.492-238G>A		intron_variant		3		ENSP00000408052

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

Gnomad4 AFR AF: 0.546

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.279

Alfa AF: 0.211 Hom.: 2419

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

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: rs2296119; hg19: chr13-46729259; COSMIC: COSV59942883; COSMIC: COSV59942883;