13-46173049-A-G

Variant names:

• chr13-46173049-A-G
• rs2209092
• NM_002298.5:c.-25+9062T>C

Variant summary

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

The NM_002298.5(LCP1):​c.-25+9062T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,160 control chromosomes in the GnomAD database, including 7,439 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 0.30 (7439 hom., cov: 32)
• Consequence: LCP1 NM_002298.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 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.-25+9062T>C		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.-25+9062T>C		intron	N/A	ENSP00000315757.2
	LCP1	ENST00000398576.6	TSL:5	c.-25+9062T>C		intron	N/A	ENSP00000381581.1
	LCP1	ENST00000442275.1	TSL:3	c.-25+9062T>C		intron	N/A	ENSP00000402157.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44875 AN: 152042 Hom.: 7417 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.295 AC: 44947 AN: 152160 Hom.: 7439 Cov.: 32 AF XY: 0.293 AC XY: 21825 AN XY: 74396

African (AFR) AF: 0.429 AC: 17809 AN: 41490

American (AMR) AF: 0.276 AC: 4222 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1007 AN: 3470

East Asian (EAS) AF: 0.345 AC: 1786 AN: 5172

South Asian (SAS) AF: 0.345 AC: 1663 AN: 4820

European-Finnish (FIN) AF: 0.145 AC: 1534 AN: 10606

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16039 AN: 67998

Other (OTH) AF: 0.310 AC: 655 AN: 2114

Alfa AF: 0.266 Hom.: 10630

Bravo AF: 0.311

Asia WGS AF: 0.346 AC: 1201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.073
DANN	Benign	0.36
PhyloP100		-1.5
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: rs2209092; hg19: chr13-46747184; COSMIC: COSV59942987; COSMIC: COSV59942987;