Variant chr5-194710-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001080478.3(LRRC14B):c.902C>G(p.Pro301Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000905 in 1,603,052 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

LRRC14B
NM_001080478.3 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.76

Variant links:

Genes affected

LRRC14B (HGNC:37268): (leucine rich repeat containing 14B) The protein encoded by this gene is a leucine-rich repeat containing protein that is a member of the PRAME family. [provided by RefSeq, Apr 2017]

LRRC14B links:

LOC124900929 (HGNC:):

LOC124900929 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC14B	NM_001080478.3 linkuse as main transcript	c.902C>G	p.Pro301Arg	missense_variant, splice_region_variant	2/2	ENST00000328278.4
LOC124900929	XR_007058670.1 linkuse as main transcript	n.18G>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC14B	ENST00000328278.4 linkuse as main transcript	c.902C>G	p.Pro301Arg	missense_variant, splice_region_variant	2/2	1	NM_001080478.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000113

AC:

AN:

239426

Hom.:

AF XY:

0.0000619

AC XY:

AN XY:

129326

show subpopulations

Gnomad AFR exome

AF:

0.000586

Gnomad AMR exome

AF:

0.000265

Gnomad ASJ exome

AF:

0.000110

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000645

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.0000744

AC:

108

AN:

1450734

Hom.:

Cov.:

AF XY:

0.0000791

AC XY:

AN XY:

720306

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.000181

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:

0.0000488

Gnomad4 OTH exome

AF:

0.000117

GnomAD4 genome

AF:

0.000243

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000159

Hom.:

Bravo

AF:

0.000329

ESP6500AA

AF:

0.000487

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000124

AC:

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

Aug 16, 2021

The c.902C>G (p.P301R) alteration is located in exon 2 (coding exon 2) of the LRRC14B gene. This alteration results from a C to G substitution at nucleotide position 902, causing the proline (P) at amino acid position 301 to be replaced by an arginine (R). 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

0.16

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.067

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.80

M_CAP

Benign

0.0088

MetaRNN

Uncertain

0.56

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.32

Sift

Uncertain

0.022

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.69

MVP

0.46

MPC

0.77

ClinPred

0.097

GERP RS

5.8

Varity_R

0.24

gMVP

0.58

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