chr13-46134156-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. K533R) has been classified as Uncertain significance.

• 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
• Publications: 39 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]

CPB2-AS1 (HGNC:39898): (CPB2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

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.1597A>G	p.Lys533Glu	missense	Exon 14 of 16	NP_002289.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCP1	ENST00000323076.7	TSL:1 MANE Select	c.1597A>G	p.Lys533Glu	missense	Exon 14 of 16	ENSP00000315757.2
	LCP1	ENST00000398576.6	TSL:5	c.1597A>G	p.Lys533Glu	missense	Exon 17 of 19	ENSP00000381581.1
	LCP1	ENST00000674665.1		c.304A>G	p.Lys102Glu	missense	Exon 3 of 5	ENSP00000501964.1

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

GnomAD2 exomes AF: 0.910 AC: 228767 AN: 251298 AF XY: 0.913

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 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

African (AFR) AF: 0.794 AC: 26560 AN: 33444

American (AMR) AF: 0.952 AC: 42565 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.893 AC: 23340 AN: 26128

East Asian (EAS) AF: 0.930 AC: 36897 AN: 39658

South Asian (SAS) AF: 0.966 AC: 83328 AN: 86244

European-Finnish (FIN) AF: 0.932 AC: 49691 AN: 53328

Middle Eastern (MID) AF: 0.911 AC: 5248 AN: 5760

European-Non Finnish (NFE) AF: 0.904 AC: 1004166 AN: 1111324

Other (OTH) AF: 0.905 AC: 54661 AN: 60368

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

African (AFR) AF: 0.785 AC: 32573 AN: 41474

American (AMR) AF: 0.912 AC: 13946 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.894 AC: 3103 AN: 3472

East Asian (EAS) AF: 0.911 AC: 4714 AN: 5176

South Asian (SAS) AF: 0.966 AC: 4664 AN: 4826

European-Finnish (FIN) AF: 0.934 AC: 9910 AN: 10614

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.900 AC: 61240 AN: 68012

Other (OTH) AF: 0.885 AC: 1871 AN: 2114

Alfa AF: 0.893 Hom.: 205679

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 v4.9

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
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
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	-0.35	N
PhyloP100		2.7
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.17	N
REVEL	Uncertain	0.29
Sift	Benign	0.10	T
Sift4G	Benign	0.099	T
Polyphen		0.0	B
Vest4		0.031
MPC		0.49
ClinPred		0.0076	T
GERP RS		4.2
Varity_R		0.10
gMVP		0.48
Mutation Taster		=97/3	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: rs4941543; hg19: chr13-46708291; COSMIC: COSV59939454;