chr13-46142283-C-A

Variant names:

• chr13-46142283-C-A
• rs80266547
• NM_002298.5:c.1502+9G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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: Benign. The variant received -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 VariationId is 790278.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 1165 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002298.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCP1	NM_002298.5	MANE Select	c.1502+9G>T		intron	N/A	NP_002289.2	P13796-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCP1	ENST00000323076.7	TSL:1 MANE Select	c.1502+9G>T		intron	N/A	ENSP00000315757.2	P13796-1
	LCP1	ENST00000398576.6	TSL:5	c.1502+9G>T		intron	N/A	ENSP00000381581.1	P13796-1
	LCP1	ENST00000903164.1		c.1502+9G>T		intron	N/A	ENSP00000573223.1

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

GnomAD2 exomes AF: 0.00662 AC: 1664 AN: 251360 AF XY: 0.00679

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 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

African (AFR) AF: 0.00170 AC: 57 AN: 33476

American (AMR) AF: 0.00313 AC: 140 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 173 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00408 AC: 351 AN: 86110

European-Finnish (FIN) AF: 0.00441 AC: 235 AN: 53334

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5764

European-Non Finnish (NFE) AF: 0.0139 AC: 15434 AN: 1111106

Other (OTH) AF: 0.0108 AC: 650 AN: 60302

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

African (AFR) AF: 0.00236 AC: 98 AN: 41544

American (AMR) AF: 0.00366 AC: 56 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00414 AC: 20 AN: 4826

European-Finnish (FIN) AF: 0.00387 AC: 41 AN: 10594

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0133 AC: 905 AN: 68026

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

Alfa AF: 0.00964 Hom.: 1

Bravo AF: 0.00683

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.16
DANN	Benign	0.33
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs80266547; hg19: chr13-46716418;