13-46142283-C-A

Position:

• chr13-46142283-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002298.5(LCP1):​c.1502+9G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,612,840 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0077 (5 hom., cov: 32)
  • Exomes 𝑓: 0.012 (144 hom.)
• Consequence: LCP1 NM_002298.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.498

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 13-46142283-C-A is Benign according to our data. Variant chr13-46142283-C-A is described in ClinVar as [Benign]. Clinvar id is 790278.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 1165 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCP1	NM_002298.5	c.1502+9G>T		intron_variant		ENST00000323076.7
LCP1	XM_005266374.3	c.1502+9G>T		intron_variant
LCP1	XM_047430303.1	c.1502+9G>T		intron_variant
LCP1	XM_047430304.1	c.1067+9G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCP1	ENST00000323076.7	c.1502+9G>T		intron_variant		1	NM_002298.5	P1
CPB2-AS1	ENST00000663159.1	n.470-9211C>A		intron_variant, non_coding_transcript_variant
LCP1	ENST00000398576.6	c.1502+9G>T		intron_variant		5		P1
LCP1	ENST00000674665.1	c.209+9G>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.00766 AC: 1165 AN: 152140 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00237

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00387

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00662 AC: 1664 AN: 251360 Hom.: 5 AF XY: 0.00679 AC XY: 922 AN XY: 135852

Gnomad AFR exome AF: 0.00135

Gnomad AMR exome AF: 0.00286

Gnomad ASJ exome AF: 0.00714

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00408

Gnomad FIN exome AF: 0.00439

Gnomad NFE exome AF: 0.0106

Gnomad OTH exome AF: 0.00652

GnomAD4 exome AF: 0.0117 AC: 17050 AN: 1460582 Hom.: 144 Cov.: 31 AF XY: 0.0114 AC XY: 8309 AN XY: 726558

Gnomad4 AFR exome AF: 0.00170

Gnomad4 AMR exome AF: 0.00313

Gnomad4 ASJ exome AF: 0.00663

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00408

Gnomad4 FIN exome AF: 0.00441

Gnomad4 NFE exome AF: 0.0139

Gnomad4 OTH exome AF: 0.0108

GnomAD4 genome AF: 0.00765 AC: 1165 AN: 152258 Hom.: 5 Cov.: 32 AF XY: 0.00707 AC XY: 526 AN XY: 74440

Gnomad4 AFR AF: 0.00236

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00414

Gnomad4 FIN AF: 0.00387

Gnomad4 NFE AF: 0.0133

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00964 Hom.: 1

Bravo AF: 0.00683

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.16
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs80266547; hg19: chr13-46716418;