chr13-46158935-G-A

Position:

• chr13-46158935-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_002298.5(LCP1):​c.119C>T​(p.Ala40Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00721 in 1,614,104 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0074 (50 hom.)
• Consequence: LCP1 NM_002298.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.37

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007674128).
• BP6: Variant 13-46158935-G-A is Benign according to our data. Variant chr13-46158935-G-A is described in ClinVar as [Benign]. Clinvar id is 718752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 750 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCP1	NM_002298.5	c.119C>T	p.Ala40Val	missense_variant	3/16	ENST00000323076.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCP1	ENST00000323076.7	c.119C>T	p.Ala40Val	missense_variant	3/16	1	NM_002298.5	P1
CPB2-AS1	ENST00000663159.1	n.1031G>A		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.00493 AC: 750 AN: 152164 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00472

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0118

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00689

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00521 AC: 1311 AN: 251436 Hom.: 5 AF XY: 0.00508 AC XY: 690 AN XY: 135882

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00257

Gnomad ASJ exome AF: 0.00516

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000490

Gnomad FIN exome AF: 0.00989

Gnomad NFE exome AF: 0.00777

Gnomad OTH exome AF: 0.00619

GnomAD4 exome AF: 0.00745 AC: 10885 AN: 1461822 Hom.: 50 Cov.: 31 AF XY: 0.00726 AC XY: 5283 AN XY: 727210

Gnomad4 AFR exome AF: 0.00102

Gnomad4 AMR exome AF: 0.00324

Gnomad4 ASJ exome AF: 0.00490

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000580

Gnomad4 FIN exome AF: 0.00972

Gnomad4 NFE exome AF: 0.00863

Gnomad4 OTH exome AF: 0.00677

GnomAD4 genome AF: 0.00493 AC: 750 AN: 152282 Hom.: 4 Cov.: 32 AF XY: 0.00493 AC XY: 367 AN XY: 74468

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00471

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0118

Gnomad4 NFE AF: 0.00689

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00645 Hom.: 4

Bravo AF: 0.00453

TwinsUK AF: 0.0111 AC: 41

ALSPAC AF: 0.0101 AC: 39

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.00802 AC: 69

ExAC AF: 0.00534 AC: 648

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00676

EpiControl AF: 0.00800

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T;T;.;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	.;D;D;D
MetaRNN	Benign	0.0077	T;T;T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.6	M;M;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Uncertain	0.30
Sift	Benign	0.18	T;T;T;T
Sift4G	Benign	0.24	T;T;T;D
Polyphen		0.45	B;B;.;.
Vest4		0.14
MVP		0.54
MPC		0.40
ClinPred		0.059	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.62
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs117014375; hg19: chr13-46733070; COSMIC: COSV100549767; COSMIC: COSV100549767;