rs4941543

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr13-46134156-T-A
• chr13-46134156-T-C
• chr13-46134156-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002298.5(LCP1):​c.1597A>T​(p.Lys533*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LCP1 NM_002298.5 stop_gained
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP1	NM_002298.5	c.1597A>T	p.Lys533*	stop_gained	Exon 14 of 16	ENST00000323076.7	NP_002289.2
LCP1	XM_005266374.3	c.1597A>T	p.Lys533*	stop_gained	Exon 14 of 16		XP_005266431.1
LCP1	XM_047430303.1	c.1597A>T	p.Lys533*	stop_gained	Exon 14 of 16		XP_047286259.1
LCP1	XM_047430304.1	c.1162A>T	p.Lys388*	stop_gained	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>T	p.Lys533*	stop_gained	Exon 14 of 16	1	NM_002298.5	ENSP00000315757.2
LCP1	ENST00000398576.6	c.1597A>T	p.Lys533*	stop_gained	Exon 17 of 19	5		ENSP00000381581.1
LCP1	ENST00000674665.1	c.304A>T	p.Lys102*	stop_gained	Exon 3 of 5			ENSP00000501964.1
CPB2-AS1	ENST00000663159.1	n.470-17338T>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461486 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 727076

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111780

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	35
DANN	Uncertain	0.97
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.26	N
PhyloP100		2.7
Vest4		0.69
GERP RS		4.2
Mutation Taster		=10/190	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;