Variant 19-50518509-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001080457.2(LRRC4B):c.1204A>T(p.Thr402Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000447 in 1,566,210 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

LRRC4B
NM_001080457.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.09

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25644898).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC4B	NM_001080457.2 linkuse as main transcript	c.1204A>T	p.Thr402Ser	missense_variant	3/3	ENST00000652263.1	NP_001073926.1
LOC124904747	XR_007067300.1 linkuse as main transcript	n.54+7038T>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.1204A>T	p.Thr402Ser	missense_variant	3/3		NM_001080457.2	ENSP00000498662	P1
LRRC4B	ENST00000389201.7 linkuse as main transcript	c.1204A>T	p.Thr402Ser	missense_variant	3/3	2		ENSP00000373853	P1
LRRC4B	ENST00000599957.5 linkuse as main transcript	c.1204A>T	p.Thr402Ser	missense_variant	3/3	3		ENSP00000471502	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000941

AC:

AN:

212484

Hom.:

AF XY:

0.00000879

AC XY:

AN XY:

113736

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000103

Gnomad OTH exome

AF:

0.000197

GnomAD4 exome

AF:

0.00000424

AC:

AN:

1414078

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

697460

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:

0.00000460

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.00000827

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

Mar 24, 2023

The c.1204A>T (p.T402S) alteration is located in exon 3 (coding exon 2) of the LRRC4B gene. This alteration results from a A to T substitution at nucleotide position 1204, causing the threonine (T) at amino acid position 402 to be replaced by a serine (S). 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

Uncertain

0.48

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Benign

0.95

DEOGEN2

Benign

0.047

T;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.016

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.79

.;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.19

N;N

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.4

.;N

REVEL

Benign

0.15

Sift

Benign

0.18

.;T

Sift4G

Benign

0.18

T;T

Polyphen

0.30

B;B

Vest4

0.13

MutPred

0.35

Gain of disorder (P = 0.106);Gain of disorder (P = 0.106);

MVP

0.65

MPC

1.1

ClinPred

0.34

GERP RS

3.7

Varity_R

0.24

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