chr13-46180599-T-C

Variant names:

• chr13-46180599-T-C
• rs9567638
• NM_002298.5:c.-25+1512A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002298.5(LCP1):​c.-25+1512A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0492 in 152,288 control chromosomes in the GnomAD database, including 296 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 0.049 (296 hom., cov: 32)
• Consequence: LCP1 NM_002298.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCP1	NM_002298.5	c.-25+1512A>G		intron_variant	Intron 1 of 15	ENST00000323076.7	NP_002289.2
LCP1	XM_005266374.3	c.-12161A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 16		XP_005266431.1
LCP1	XM_005266374.3	c.-12161A>G		5_prime_UTR_variant	Exon 1 of 16		XP_005266431.1
LCP1	XM_047430305.1	c.-25+1512A>G		intron_variant	Intron 1 of 8		XP_047286261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCP1	ENST00000323076.7	c.-25+1512A>G		intron_variant	Intron 1 of 15	1	NM_002298.5	ENSP00000315757.2
LCP1	ENST00000398576.6	c.-25+1512A>G		intron_variant	Intron 4 of 18	5		ENSP00000381581.1
LCP1	ENST00000442275.1	c.-25+1512A>G		intron_variant	Intron 5 of 6	3		ENSP00000402157.1
LCP1	ENST00000460190.1	n.94+1512A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7456 AN: 152170 Hom.: 291 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0263

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.0517

Gnomad SAS AF: 0.0753

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0483

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

GnomAD4 genome AF: 0.0492 AC: 7488 AN: 152288 Hom.: 296 Cov.: 32 AF XY: 0.0487 AC XY: 3629 AN XY: 74482

African (AFR) AF: 0.110 AC: 4571 AN: 41550

American (AMR) AF: 0.0263 AC: 402 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0634 AC: 220 AN: 3470

East Asian (EAS) AF: 0.0511 AC: 265 AN: 5190

South Asian (SAS) AF: 0.0752 AC: 363 AN: 4828

European-Finnish (FIN) AF: 0.0143 AC: 152 AN: 10614

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0203 AC: 1379 AN: 68018

Other (OTH) AF: 0.0544 AC: 115 AN: 2114

Alfa AF: 0.0334 Hom.: 102

Bravo AF: 0.0507

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.4
DANN	Benign	0.75
PhyloP100		-0.017
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs9567638; hg19: chr13-46754734;