13-46172994-T-C

Variant names:

• chr13-46172994-T-C
• rs2209093
• NM_002298.5:c.-25+9117A>G

Variant summary

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

The NM_002298.5(LCP1):​c.-25+9117A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,102 control chromosomes in the GnomAD database, including 2,649 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 0.18 (2649 hom., cov: 32)
• Consequence: LCP1 NM_002298.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP1	NM_002298.5	c.-25+9117A>G		intron_variant	Intron 1 of 15	ENST00000323076.7	NP_002289.2
LCP1	XM_005266374.3	c.-4556A>G		5_prime_UTR_variant	Exon 1 of 16		XP_005266431.1
LCP1	XM_047430305.1	c.-25+9117A>G		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+9117A>G		intron_variant	Intron 1 of 15	1	NM_002298.5	ENSP00000315757.2
LCP1	ENST00000398576.6	c.-25+9117A>G		intron_variant	Intron 4 of 18	5		ENSP00000381581.1
LCP1	ENST00000442275.1	c.-25+9117A>G		intron_variant	Intron 5 of 6	3		ENSP00000402157.1
LCP1	ENST00000460190.1	n.94+9117A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26842 AN: 151986 Hom.: 2643 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.177 AC: 26873 AN: 152102 Hom.: 2649 Cov.: 32 AF XY: 0.176 AC XY: 13097 AN XY: 74344

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.214

Alfa AF: 0.183 Hom.: 1367

Bravo AF: 0.184

Asia WGS AF: 0.294 AC: 1021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.75
DANN	Benign	0.47

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: rs2209093; hg19: chr13-46747129; COSMIC: COSV59942980; COSMIC: COSV59942980;