Variant 8-144520483-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014665.4(LRRC14):c.575C>T(p.Pro192Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000375 in 1,597,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

LRRC14
NM_014665.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

Variant links:

Genes affected

LRRC14 (HGNC:20419): (leucine rich repeat containing 14) This gene encodes a leucine-rich repeat-containing protein. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

LRRC14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08984801).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC14	NM_014665.4 linkuse as main transcript	c.575C>T	p.Pro192Leu	missense_variant	3/4	ENST00000292524.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LRRC14	ENST00000292524.6 linkuse as main transcript	c.575C>T	p.Pro192Leu	missense_variant	3/4	1	NM_014665.4	P1
LRRC14	ENST00000529022.5 linkuse as main transcript	c.575C>T	p.Pro192Leu	missense_variant	4/5	1		P1
LRRC14	ENST00000527730.1 linkuse as main transcript	c.575C>T	p.Pro192Leu	missense_variant	3/3	2
LRRC14	ENST00000531310.1 linkuse as main transcript	n.1030C>T		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000380

AC:

AN:

236624

Hom.:

AF XY:

0.0000463

AC XY:

AN XY:

129514

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.0000761

Gnomad NFE exome

AF:

0.0000550

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000367

AC:

AN:

1445762

Hom.:

Cov.:

AF XY:

0.0000445

AC XY:

AN XY:

719162

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000744

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000836

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000498

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.575C>T (p.P192L) alteration is located in exon 3 (coding exon 2) of the LRRC14 gene. This alteration results from a C to T substitution at nucleotide position 575, causing the proline (P) at amino acid position 192 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.52

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.70

T;.;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.090

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-4.1

D;D;D

REVEL

Benign

0.081

Sift

Uncertain

0.025

D;D;D

Sift4G

Uncertain

0.010

D;D;D

Polyphen

0.094

.;B;B

Vest4

0.35, 0.35

MVP

0.27

MPC

0.48

ClinPred

0.12

GERP RS

2.5

Varity_R

0.15

gMVP

0.67

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over