Variant chr8-144520491-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014665.4(LRRC14):c.583C>G(p.Leu195Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LRRC14
NM_014665.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.75

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:

LRRC14 (HGNC:):

LRRC14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38392735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC14	NM_014665.4 linkuse as main transcript	c.583C>G	p.Leu195Val	missense_variant	3/4	ENST00000292524.6	NP_055480.1	Q15048

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRRC14	ENST00000292524.6 linkuse as main transcript	c.583C>G	p.Leu195Val	missense_variant	3/4	1	NM_014665.4	ENSP00000292524.1	Q15048
LRRC14	ENST00000529022.5 linkuse as main transcript	c.583C>G	p.Leu195Val	missense_variant	4/5	1		ENSP00000434768.1	Q15048
LRRC14	ENST00000527730.1 linkuse as main transcript	c.583C>G	p.Leu195Val	missense_variant	3/3	2		ENSP00000436452.1	E9PP40
LRRC14	ENST00000531310.1 linkuse as main transcript	n.1038C>G		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1446164

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719536

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 22, 2024

The c.583C>G (p.L195V) alteration is located in exon 3 (coding exon 2) of the LRRC14 gene. This alteration results from a C to G substitution at nucleotide position 583, causing the leucine (L) at amino acid position 195 to be replaced by a valine (V). 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

0.23

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;T;T

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.80

T;.;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.38

T;T;T

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.0

.;M;M

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.19

Sift

Benign

0.13

T;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.75

MutPred

0.37

Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);

MVP

0.65

MPC

1.3

ClinPred

0.88

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.69

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over