rs10492449

Variant names:

• chr13-46181745-T-G
• rs10492449
• NM_002298.5:c.-25+366A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002298.5(LCP1):​c.-25+366A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,252 control chromosomes in the GnomAD database, including 4,449 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 0.21 (4449 hom., cov: 32)
• Consequence: LCP1 NM_002298.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP1	NM_002298.5	c.-25+366A>C		intron_variant	Intron 1 of 15	ENST00000323076.7	NP_002289.2
LCP1	XM_005266374.3	c.-13307A>C		5_prime_UTR_variant	Exon 1 of 16		XP_005266431.1
LCP1	XM_047430305.1	c.-25+366A>C		intron_variant	Intron 1 of 8		XP_047286261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP1	ENST00000323076.7	c.-25+366A>C		intron_variant	Intron 1 of 15	1	NM_002298.5	ENSP00000315757.2
LCP1	ENST00000398576.6	c.-25+366A>C		intron_variant	Intron 4 of 18	5		ENSP00000381581.1
LCP1	ENST00000442275.1	c.-25+366A>C		intron_variant	Intron 5 of 6	3		ENSP00000402157.1
LCP1	ENST00000460190.1	n.94+366A>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32260 AN: 152134 Hom.: 4451 Cov.: 32

Gnomad AFR AF: 0.0588

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.0280

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.212 AC: 32244 AN: 152252 Hom.: 4449 Cov.: 32 AF XY: 0.208 AC XY: 15461 AN XY: 74434

African (AFR) AF: 0.0587 AC: 2439 AN: 41552

American (AMR) AF: 0.178 AC: 2726 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 914 AN: 3470

East Asian (EAS) AF: 0.0281 AC: 146 AN: 5194

South Asian (SAS) AF: 0.180 AC: 867 AN: 4826

European-Finnish (FIN) AF: 0.283 AC: 2997 AN: 10592

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21384 AN: 67996

Other (OTH) AF: 0.215 AC: 455 AN: 2114

Alfa AF: 0.268 Hom.: 17981

Bravo AF: 0.193

Asia WGS AF: 0.104 AC: 363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	15
DANN	Benign	0.71
PhyloP100		1.6
PromoterAI		-0.036	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs10492449; hg19: chr13-46755880;