Variant 19-50518345-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001080457.2(LRRC4B):c.1368G>T(p.Val456Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00744 in 1,606,032 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0060 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 68 hom. )

Consequence

LRRC4B
NM_001080457.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.480

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 19-50518345-C-A is Benign according to our data. Variant chr19-50518345-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2650352.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.48 with no splicing effect.

BS2

High AC in GnomAd4 at 912 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC4B	NM_001080457.2 linkuse as main transcript	c.1368G>T	p.Val456Val	synonymous_variant	3/3	ENST00000652263.1	NP_001073926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRRC4B	ENST00000652263.1 linkuse as main transcript	c.1368G>T	p.Val456Val	synonymous_variant	3/3		NM_001080457.2	ENSP00000498662.1	Q9NT99
LRRC4B	ENST00000389201.7 linkuse as main transcript	c.1368G>T	p.Val456Val	synonymous_variant	3/3	2		ENSP00000373853.3	Q9NT99
LRRC4B	ENST00000599957.5 linkuse as main transcript	c.1368G>T	p.Val456Val	synonymous_variant	3/3	3		ENSP00000471502.1	Q9NT99

Frequencies

GnomAD3 genomes

AF:

0.00600

AC:

913

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00392

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0196

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00835

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00672

AC:

1599

AN:

237780

Hom.:

AF XY:

0.00659

AC XY:

858

AN XY:

130172

show subpopulations

Gnomad AFR exome

AF:

0.00101

Gnomad AMR exome

AF:

0.00276

Gnomad ASJ exome

AF:

0.000105

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00101

Gnomad FIN exome

AF:

0.0188

Gnomad NFE exome

AF:

0.00966

Gnomad OTH exome

AF:

0.00912

GnomAD4 exome

AF:

0.00759

AC:

11038

AN:

1453686

Hom.:

Cov.:

AF XY:

0.00735

AC XY:

5313

AN XY:

722896

show subpopulations

Gnomad4 AFR exome

AF:

0.000662

Gnomad4 AMR exome

AF:

0.00284

Gnomad4 ASJ exome

AF:

0.0000776

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000923

Gnomad4 FIN exome

AF:

0.0206

Gnomad4 NFE exome

AF:

0.00846

Gnomad4 OTH exome

AF:

0.00626

GnomAD4 genome

AF:

0.00599

AC:

912

AN:

152346

Hom.:

Cov.:

AF XY:

0.00604

AC XY:

450

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0196

Gnomad4 NFE

AF:

0.00833

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00569

Hom.:

Bravo

AF:

0.00451

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00583

EpiControl

AF:

0.00712

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

LRRC4B: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.89

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