Variant 19-50518947-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001080457.2(LRRC4B):c.766C>T(p.Arg256Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,596 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LRRC4B
NM_001080457.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.90

Variant links:

Genes affected

LRRC4B (HGNC:25042): (leucine rich repeat containing 4B) Predicted to enable signaling receptor binding activity. Predicted to be involved in regulation of synapse assembly and synaptic membrane adhesion. Predicted to be located in cerebellar mossy fiber and presynaptic membrane. Predicted to be active in glutamatergic synapse and plasma membrane. Predicted to be integral component of postsynaptic density membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC4B links:

LOC124904747 (HGNC:):

LOC124904747 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	Protein	UniProt
LRRC4B	NM_001080457.2 linkuse as main transcript	c.766C>T	p.Arg256Cys	missense_variant	3/3	ENST00000652263.1	NP_001073926.1
LOC124904747	XR_007067300.1 linkuse as main transcript	n.54+7476G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LRRC4B	ENST00000652263.1 linkuse as main transcript	c.766C>T	p.Arg256Cys	missense_variant	3/3		NM_001080457.2	ENSP00000498662	P1
LRRC4B	ENST00000389201.7 linkuse as main transcript	c.766C>T	p.Arg256Cys	missense_variant	3/3	2		ENSP00000373853	P1
LRRC4B	ENST00000599957.5 linkuse as main transcript	c.766C>T	p.Arg256Cys	missense_variant	3/3	3		ENSP00000471502	P1
LRRC4B	ENST00000600381.1 linkuse as main transcript			downstream_gene_variant		2		ENSP00000472528

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247616

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134682

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461596

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727148

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

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

Feb 27, 2023

The c.766C>T (p.R256C) alteration is located in exon 3 (coding exon 2) of the LRRC4B gene. This alteration results from a C to T substitution at nucleotide position 766, causing the arginine (R) at amino acid position 256 to be replaced by a cysteine (C). 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

Pathogenic

0.86

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.26

T;T

Eigen

Pathogenic

0.72

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.84

LIST_S2

Pathogenic

0.98

.;D

M_CAP

Benign

0.052

MetaRNN

Uncertain

0.59

D;D

MetaSVM

Uncertain

-0.098

MutationAssessor

Pathogenic

3.0

M;M

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-5.3

.;D

REVEL

Uncertain

0.51

Sift

Uncertain

0.0010

.;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.49

MutPred

0.53

Loss of MoRF binding (P = 0.0279);Loss of MoRF binding (P = 0.0279);

MVP

0.88

MPC

2.6

ClinPred

0.99

GERP RS

4.0

Varity_R

0.54

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