rs17601960

Positions:

• chr13-46176746-T-C

Variant summary

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

The NM_002298.5(LCP1):​c.-25+5365A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0537 in 152,326 control chromosomes in the GnomAD database, including 300 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 0.054 (300 hom., cov: 33)
• Consequence: LCP1 NM_002298.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCP1	NM_002298.5	c.-25+5365A>G		intron_variant		ENST00000323076.7
LCP1	XM_005266374.3	c.-8308A>G		5_prime_UTR_variant	1/16
LCP1	XM_047430305.1	c.-25+5365A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCP1	ENST00000323076.7	c.-25+5365A>G		intron_variant		1	NM_002298.5	P1
LCP1	ENST00000398576.6	c.-25+5365A>G		intron_variant		5		P1
LCP1	ENST00000442275.1	c.-25+5365A>G		intron_variant		3
LCP1	ENST00000460190.1	n.94+5365A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8183 AN: 152208 Hom.: 300 Cov.: 33

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0383

Gnomad ASJ AF: 0.0626

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0775

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0772

Gnomad OTH AF: 0.0602

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

GnomAD4 genome AF: 0.0537 AC: 8181 AN: 152326 Hom.: 300 Cov.: 33 AF XY: 0.0544 AC XY: 4052 AN XY: 74484

Gnomad4 AFR AF: 0.0143

Gnomad4 AMR AF: 0.0384

Gnomad4 ASJ AF: 0.0626

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0997

Gnomad4 FIN AF: 0.0775

Gnomad4 NFE AF: 0.0772

Gnomad4 OTH AF: 0.0601

Alfa AF: 0.0708 Hom.: 540

Bravo AF: 0.0471

Asia WGS AF: 0.0320 AC: 112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Benign	0.81

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: rs17601960; hg19: chr13-46750881;