chr13-46126507-G-T

Position:

• chr13-46126507-G-T

Variant summary

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

The NM_002298.5(LCP1):​c.*1084C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 232,068 control chromosomes in the GnomAD database, including 20,232 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 0.40 (12123 hom., cov: 32)
  • Exomes 𝑓: 0.45 (8109 hom.)
• Consequence: LCP1 NM_002298.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219

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 (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCP1	NM_002298.5	c.*1084C>A		3_prime_UTR_variant	16/16	ENST00000323076.7
LCP1	XM_005266374.3	c.*1084C>A		3_prime_UTR_variant	16/16
LCP1	XM_047430303.1	c.*1084C>A		3_prime_UTR_variant	16/16
LCP1	XM_047430304.1	c.*1084C>A		3_prime_UTR_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCP1	ENST00000323076.7	c.*1084C>A		3_prime_UTR_variant	16/16	1	NM_002298.5	P1
CPB2-AS1	ENST00000663159.1	n.470-24987G>T		intron_variant, non_coding_transcript_variant
LCP1	ENST00000398576.6	c.*1084C>A		3_prime_UTR_variant	19/19	5		P1
LCP1	ENST00000674665.1	c.*1084C>A		3_prime_UTR_variant	5/5

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60146 AN: 151900 Hom.: 12126 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.458

GnomAD4 exome AF: 0.446 AC: 35735 AN: 80048 Hom.: 8109 Cov.: 0 AF XY: 0.451 AC XY: 16647 AN XY: 36928

Gnomad4 AFR exome AF: 0.317

Gnomad4 AMR exome AF: 0.408

Gnomad4 ASJ exome AF: 0.457

Gnomad4 EAS exome AF: 0.497

Gnomad4 SAS exome AF: 0.471

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.447

Gnomad4 OTH exome AF: 0.443

GnomAD4 genome AF: 0.396 AC: 60159 AN: 152020 Hom.: 12123 Cov.: 32 AF XY: 0.396 AC XY: 29416 AN XY: 74316

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.459

Alfa AF: 0.325 Hom.: 1576

Bravo AF: 0.398

Asia WGS AF: 0.469 AC: 1627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.3
DANN	Benign	0.86

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: rs11342; hg19: chr13-46700642; COSMIC: COSV59942843; COSMIC: COSV59942843;