Variant 1-165563711-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001005214.4(LRRC52):c.829C>T(p.Arg277Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,614,130 control chromosomes in the GnomAD database, including 128 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 0.0096 ( 13 hom., cov: 32)

Exomes 𝑓: 0.012 ( 115 hom. )

Consequence

LRRC52
NM_001005214.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.298

Variant links:

Genes affected

LRRC52 (HGNC:32156): (leucine rich repeat containing 52) Enables potassium channel activator activity; transmembrane transporter binding activity; and voltage-gated potassium channel activity. Involved in positive regulation of voltage-gated potassium channel activity and potassium ion transmembrane transport. Part of voltage-gated potassium channel complex. [provided by Alliance of Genome Resources, Apr 2022]

LRRC52 links:

LRRC52-AS1 (HGNC:54044): (LRRC52 antisense RNA 1)

LRRC52-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005638212).

BP6

Variant 1-165563711-C-T is Benign according to our data. Variant chr1-165563711-C-T is described in ClinVar as [Benign]. Clinvar id is 783012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC52	NM_001005214.4 linkuse as main transcript	c.829C>T	p.Arg277Cys	missense_variant	2/2	ENST00000294818.2
LRRC52-AS1	NR_026744.2 linkuse as main transcript	n.959+10307G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC52	ENST00000294818.2 linkuse as main transcript	c.829C>T	p.Arg277Cys	missense_variant	2/2	1	NM_001005214.4	P1
LRRC52-AS1	ENST00000416424.5 linkuse as main transcript	n.872+10307G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00956

AC:

1454

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00949

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00684

Gnomad FIN

AF:

0.0131

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0144

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.00973

AC:

2447

AN:

251402

Hom.:

AF XY:

0.0102

AC XY:

1383

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.00986

Gnomad ASJ exome

AF:

0.00625

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00637

Gnomad FIN exome

AF:

0.0123

Gnomad NFE exome

AF:

0.0130

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.0124

AC:

18161

AN:

1461884

Hom.:

115

Cov.:

AF XY:

0.0124

AC XY:

8990

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00248

Gnomad4 AMR exome

AF:

0.00961

Gnomad4 ASJ exome

AF:

0.00616

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00671

Gnomad4 FIN exome

AF:

0.0123

Gnomad4 NFE exome

AF:

0.0140

Gnomad4 OTH exome

AF:

0.0112

GnomAD4 genome

AF:

0.00955

AC:

1454

AN:

152246

Hom.:

Cov.:

AF XY:

0.00936

AC XY:

697

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00250

Gnomad4 AMR

AF:

0.00948

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00685

Gnomad4 FIN

AF:

0.0131

Gnomad4 NFE

AF:

0.0144

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.0126

Hom.:

Bravo

AF:

0.00889

TwinsUK

AF:

0.0148

AC:

ALSPAC

AF:

0.0112

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0155

AC:

133

ExAC

AF:

0.00975

AC:

1184

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0136

EpiControl

AF:

0.0148

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.12

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0056

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

0.090

REVEL

Benign

0.026

Sift

Benign

0.20

Sift4G

Benign

0.090

Polyphen

0.016

Vest4

0.14

MVP

0.56

MPC

0.26

ClinPred

0.0046

GERP RS

0.94

Varity_R

0.051

gMVP

0.38

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