rs1409437

Positions:

• chr13-46130078-A-G

Variant summary

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

The NM_002298.5(LCP1):​c.1751+736T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,106 control chromosomes in the GnomAD database, including 11,070 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 0.37 (11070 hom., cov: 32)
• Consequence: LCP1 NM_002298.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691

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:):

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 (EAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCP1	NM_002298.5	c.1751+736T>C		intron_variant		ENST00000323076.7	NP_002289.2
LCP1	XM_005266374.3	c.1751+736T>C		intron_variant			XP_005266431.1
LCP1	XM_047430303.1	c.1751+736T>C		intron_variant			XP_047286259.1
LCP1	XM_047430304.1	c.1316+736T>C		intron_variant			XP_047286260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCP1	ENST00000323076.7	c.1751+736T>C		intron_variant		1	NM_002298.5	ENSP00000315757.2
LCP1	ENST00000398576.6	c.1751+736T>C		intron_variant		5		ENSP00000381581.1
LCP1	ENST00000674665.1	c.458+736T>C		intron_variant				ENSP00000501964.1
CPB2-AS1	ENST00000663159.1	n.470-21416A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55858 AN: 151988 Hom.: 11078 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.441

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.367 AC: 55840 AN: 152106 Hom.: 11070 Cov.: 32 AF XY: 0.368 AC XY: 27400 AN XY: 74358

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.441

Alfa AF: 0.423 Hom.: 7086

Bravo AF: 0.365

Asia WGS AF: 0.474 AC: 1646 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	0.29
DANN	Benign	0.63

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: rs1409437; hg19: chr13-46704213;