13-46134156-T-C

Variant names:

• chr13-46134156-T-C
• rs4941543
• NM_002298.5:c.1597A>G

Variant summary

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

The NM_002298.5(LCP1):​c.1597A>G​(p.Lys533Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 1,613,158 control chromosomes in the GnomAD database, including 661,210 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.87 (58436 hom., cov: 31)
  • Exomes 𝑓: 0.91 (602774 hom.)
• Consequence: LCP1 NM_002298.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67

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 (MetaRNN=8.141835E-7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP1	NM_002298.5	c.1597A>G	p.Lys533Glu	missense_variant	Exon 14 of 16	ENST00000323076.7	NP_002289.2
LCP1	XM_005266374.3	c.1597A>G	p.Lys533Glu	missense_variant	Exon 14 of 16		XP_005266431.1
LCP1	XM_047430303.1	c.1597A>G	p.Lys533Glu	missense_variant	Exon 14 of 16		XP_047286259.1
LCP1	XM_047430304.1	c.1162A>G	p.Lys388Glu	missense_variant	Exon 12 of 14		XP_047286260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP1	ENST00000323076.7	c.1597A>G	p.Lys533Glu	missense_variant	Exon 14 of 16	1	NM_002298.5	ENSP00000315757.2
LCP1	ENST00000398576.6	c.1597A>G	p.Lys533Glu	missense_variant	Exon 17 of 19	5		ENSP00000381581.1
LCP1	ENST00000674665.1	c.304A>G	p.Lys102Glu	missense_variant	Exon 3 of 5			ENSP00000501964.1
CPB2-AS1	ENST00000663159.1	n.470-17338T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.875 AC: 132999 AN: 152068 Hom.: 58394 Cov.: 31

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.905

Gnomad AMR AF: 0.912

Gnomad ASJ AF: 0.894

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.966

Gnomad FIN AF: 0.934

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.883

GnomAD3 exomes AF: 0.910 AC: 228767 AN: 251298 Hom.: 104361 AF XY: 0.913 AC XY: 124057 AN XY: 135822

Gnomad AFR exome AF: 0.783

Gnomad AMR exome AF: 0.954

Gnomad ASJ exome AF: 0.895

Gnomad EAS exome AF: 0.899

Gnomad SAS exome AF: 0.966

Gnomad FIN exome AF: 0.934

Gnomad NFE exome AF: 0.899

Gnomad OTH exome AF: 0.914

GnomAD4 exome AF: 0.908 AC: 1326456 AN: 1460972 Hom.: 602774 Cov.: 40 AF XY: 0.909 AC XY: 660998 AN XY: 726846

Gnomad4 AFR exome AF: 0.794

Gnomad4 AMR exome AF: 0.952

Gnomad4 ASJ exome AF: 0.893

Gnomad4 EAS exome AF: 0.930

Gnomad4 SAS exome AF: 0.966

Gnomad4 FIN exome AF: 0.932

Gnomad4 NFE exome AF: 0.904

Gnomad4 OTH exome AF: 0.905

GnomAD4 genome AF: 0.875 AC: 133100 AN: 152186 Hom.: 58436 Cov.: 31 AF XY: 0.879 AC XY: 65370 AN XY: 74404

Gnomad4 AFR AF: 0.785

Gnomad4 AMR AF: 0.912

Gnomad4 ASJ AF: 0.894

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.966

Gnomad4 FIN AF: 0.934

Gnomad4 NFE AF: 0.900

Gnomad4 OTH AF: 0.885

Alfa AF: 0.897 Hom.: 151456

Bravo AF: 0.868

TwinsUK AF: 0.898 AC: 3328

ALSPAC AF: 0.905 AC: 3488

ESP6500AA AF: 0.798 AC: 3517

ESP6500EA AF: 0.903 AC: 7762

ExAC AF: 0.906 AC: 109959

Asia WGS AF: 0.931 AC: 3233 AN: 3478

EpiCase AF: 0.898

EpiControl AF: 0.898

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	12
DANN	Benign	0.77
DEOGEN2	Uncertain	0.47	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.19	.;T
MetaRNN	Benign	8.1e-7	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	-0.35	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.17	N;N
REVEL	Uncertain	0.29
Sift	Benign	0.10	T;T
Sift4G	Benign	0.099	T;T
Polyphen		0.0	B;B
Vest4		0.031
MPC		0.49
ClinPred		0.0076	T
GERP RS		4.2
Varity_R		0.10
gMVP		0.48

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: rs4941543; hg19: chr13-46708291; COSMIC: COSV59939454;