rs17067725

Variant names:

• chr13-46130935-G-A
• rs17067725
• NM_002298.5:c.1630C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-46130935-G-A
• chr13-46130935-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_002298.5(LCP1):​c.1630C>T​(p.Pro544Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,445,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. P544A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: LCP1 NM_002298.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12713146).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP1	NM_002298.5	c.1630C>T	p.Pro544Ser	missense_variant	Exon 15 of 16	ENST00000323076.7	NP_002289.2
LCP1	XM_005266374.3	c.1630C>T	p.Pro544Ser	missense_variant	Exon 15 of 16		XP_005266431.1
LCP1	XM_047430303.1	c.1630C>T	p.Pro544Ser	missense_variant	Exon 15 of 16		XP_047286259.1
LCP1	XM_047430304.1	c.1195C>T	p.Pro399Ser	missense_variant	Exon 13 of 14		XP_047286260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP1	ENST00000323076.7	c.1630C>T	p.Pro544Ser	missense_variant	Exon 15 of 16	1	NM_002298.5	ENSP00000315757.2
LCP1	ENST00000398576.6	c.1630C>T	p.Pro544Ser	missense_variant	Exon 18 of 19	5		ENSP00000381581.1
LCP1	ENST00000674665.1	c.337C>T	p.Pro113Ser	missense_variant	Exon 4 of 5			ENSP00000501964.1
CPB2-AS1	ENST00000663159.1	n.470-20559G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1445164 Hom.: 0 Cov.: 31 AF XY: 0.00000278 AC XY: 2 AN XY: 718476

Gnomad4 AFR exome AF: 0.0000309

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000670

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Benign	0.47
DEOGEN2	Pathogenic	0.80	D;D
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.85	.;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	0.58	N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.24
Sift	Benign	0.41	T;T
Sift4G	Benign	0.76	T;T
Polyphen		0.0	B;B
Vest4		0.082
MutPred		0.40		Gain of catalytic residue at K545 (P = 0.0362);Gain of catalytic residue at K545 (P = 0.0362);
MVP		0.44
MPC		0.35
ClinPred		0.034	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.071
gMVP		0.33

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: rs17067725; hg19: chr13-46705070;