rs144525570

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_198075.4(LRRC56):c.56G>A(p.Arg19Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,612,038 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 17 hom. )

Consequence

LRRC56
NM_198075.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.92

Variant links:

Genes affected

LRRC56 (HGNC:25430): (leucine rich repeat containing 56) Predicted to be involved in cell projection organization. Predicted to be located in cilium. Implicated in primary ciliary dyskinesia 39. [provided by Alliance of Genome Resources, Apr 2022]

LRRC56 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004208058).

BP6

Variant 11-540740-G-A is Benign according to our data. Variant chr11-540740-G-A is described in ClinVar as [Benign]. Clinvar id is 1618879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00365 (556/152224) while in subpopulation AFR AF= 0.00883 (367/41562). AF 95% confidence interval is 0.00809. There are 1 homozygotes in gnomad4. There are 264 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC56	NM_198075.4 link	c.56G>A	p.Arg19Gln	missense_variant	Exon 4 of 14	ENST00000270115.8	NP_932341.1	Q8IYG6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC56	ENST00000270115.8 link	c.56G>A	p.Arg19Gln	missense_variant	Exon 4 of 14	1	NM_198075.4	ENSP00000270115.7		Q8IYG6

Frequencies

GnomAD3 genomes

AF:

0.00366

AC:

556

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00886

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00374

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00146

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00205

AC:

506

AN:

246454

Hom.:

AF XY:

0.00206

AC XY:

276

AN XY:

133666

show subpopulations

Gnomad AFR exome

AF:

0.00851

Gnomad AMR exome

AF:

0.00239

Gnomad ASJ exome

AF:

0.00101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00119

Gnomad FIN exome

AF:

0.0000491

Gnomad NFE exome

AF:

0.00196

Gnomad OTH exome

AF:

0.00382

GnomAD4 exome

AF:

0.00157

AC:

2287

AN:

1459814

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

1167

AN XY:

726092

show subpopulations

Gnomad4 AFR exome

AF:

0.00968

Gnomad4 AMR exome

AF:

0.00273

Gnomad4 ASJ exome

AF:

0.000729

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00110

Gnomad4 FIN exome

AF:

0.0000958

Gnomad4 NFE exome

AF:

0.00126

Gnomad4 OTH exome

AF:

0.00328

GnomAD4 genome

AF:

0.00365

AC:

556

AN:

152224

Hom.:

Cov.:

AF XY:

0.00355

AC XY:

264

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00883

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00331

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00146

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00241

Hom.:

Bravo

AF:

0.00393

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00726

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00223

AC:

270

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00267

EpiControl

AF:

0.00310

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 25, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

LRRC56-related disorder

Benign:1

Feb 22, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.078

DANN

Benign

0.88

DEOGEN2

Benign

0.0027

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0072

LIST_S2

Benign

0.60

M_CAP

Benign

0.0031

MetaRNN

Benign

0.0042

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.52

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.76

REVEL

Benign

0.011

Sift

Benign

0.35

Sift4G

Benign

0.28

Polyphen

0.018

Vest4

0.050

MVP

0.13

ClinPred

0.0033

GERP RS

-5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.037

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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