rs7321994

Positions:

• chr13-46168404-G-A

Variant summary

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

The NM_002298.5(LCP1):​c.-24-8718C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,092 control chromosomes in the GnomAD database, including 7,238 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 (7238 hom., cov: 32)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: LCP1 NM_002298.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

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]

LCP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCP1	NM_002298.5	c.-24-8718C>T		intron_variant		ENST00000323076.7	NP_002289.2
LCP1	XM_005266374.3	c.-25+59C>T		intron_variant			XP_005266431.1
LCP1	XM_047430305.1	c.-24-8718C>T		intron_variant			XP_047286261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCP1	ENST00000323076.7	c.-24-8718C>T		intron_variant		1	NM_002298.5	ENSP00000315757.2

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42736 AN: 151964 Hom.: 7210 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.284

GnomAD4 exome AF: 0.100 AC: 1 AN: 10 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 NFE exome AF: 0.100

GnomAD4 genome AF: 0.282 AC: 42816 AN: 152082 Hom.: 7238 Cov.: 32 AF XY: 0.277 AC XY: 20624 AN XY: 74348

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.285

Alfa AF: 0.223 Hom.: 5363

Bravo AF: 0.301

Asia WGS AF: 0.295 AC: 1025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.097
DANN	Benign	0.55

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: rs7321994; hg19: chr13-46742539; COSMIC: COSV59942934; COSMIC: COSV59942934;