rs2093707

Positions:

• chr13-46140750-C-A
• chr13-46140750-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.1502+1542G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,984 control chromosomes in the GnomAD database, including 26,611 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 (26611 hom., cov: 32)
• Consequence: LCP1 NM_002298.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCP1	NM_002298.5	c.1502+1542G>T		intron_variant		ENST00000323076.7	NP_002289.2
LCP1	XM_005266374.3	c.1502+1542G>T		intron_variant			XP_005266431.1
LCP1	XM_047430303.1	c.1502+1542G>T		intron_variant			XP_047286259.1
LCP1	XM_047430304.1	c.1067+1542G>T		intron_variant			XP_047286260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCP1	ENST00000323076.7	c.1502+1542G>T		intron_variant		1	NM_002298.5	ENSP00000315757	P1
CPB2-AS1	ENST00000663159.1	n.470-10744C>A		intron_variant, non_coding_transcript_variant
LCP1	ENST00000398576.6	c.1502+1542G>T		intron_variant		5		ENSP00000381581	P1
LCP1	ENST00000674665.1	c.209+1542G>T		intron_variant				ENSP00000501964

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87950 AN: 151866 Hom.: 26558 Cov.: 32

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.579 AC: 88068 AN: 151984 Hom.: 26611 Cov.: 32 AF XY: 0.579 AC XY: 43031 AN XY: 74290

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.493

Gnomad4 OTH AF: 0.518

Alfa AF: 0.492 Hom.: 7978

Bravo AF: 0.581

Asia WGS AF: 0.475 AC: 1651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2093707; hg19: chr13-46714885;