Variant 1-74041358-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001105659.2(LRRIQ3):c.1573C>T(p.Arg525Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00089 in 1,613,696 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R525H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0039 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00058 ( 4 hom. )

Consequence

LRRIQ3
NM_001105659.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.41

Variant links:

Genes affected

LRRIQ3 (HGNC:28318): (leucine rich repeats and IQ motif containing 3)

LRRIQ3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005848795).

BP6

Variant 1-74041358-G-A is Benign according to our data. Variant chr1-74041358-G-A is described in ClinVar as [Benign]. Clinvar id is 3050772.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRIQ3	NM_001105659.2 linkuse as main transcript	c.1573C>T	p.Arg525Cys	missense_variant	7/8	ENST00000354431.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRIQ3	ENST00000354431.9 linkuse as main transcript	c.1573C>T	p.Arg525Cys	missense_variant	7/8	5	NM_001105659.2	P2	A6PVS8-1
LRRIQ3	ENST00000395089.5 linkuse as main transcript	c.1573C>T	p.Arg525Cys	missense_variant	6/7	5		P2	A6PVS8-1
LRRIQ3	ENST00000417067.5 linkuse as main transcript	c.131-14389C>T		intron_variant		2
LRRIQ3	ENST00000415760.5 linkuse as main transcript	c.*2703+333C>T		intron_variant, NMD_transcript_variant		2			A6PVS8-2

Frequencies

GnomAD3 genomes

AF:

0.00384

AC:

584

AN:

151950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00125

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00107

AC:

267

AN:

248878

Hom.:

AF XY:

0.000978

AC XY:

132

AN XY:

135018

show subpopulations

Gnomad AFR exome

AF:

0.0117

Gnomad AMR exome

AF:

0.000638

Gnomad ASJ exome

AF:

0.00259

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.000275

Gnomad OTH exome

AF:

0.000497

GnomAD4 exome

AF:

0.000581

AC:

849

AN:

1461628

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

401

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.0131

Gnomad4 AMR exome

AF:

0.000894

Gnomad4 ASJ exome

AF:

0.00222

Gnomad4 EAS exome

AF:

0.00103

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000183

Gnomad4 OTH exome

AF:

0.000878

GnomAD4 genome

AF:

0.00386

AC:

587

AN:

152068

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

262

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0130

Gnomad4 AMR

AF:

0.00125

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000900

Hom.:

Bravo

AF:

0.00422

ESP6500AA

AF:

0.0114

AC:

ESP6500EA

AF:

0.000736

AC:

ExAC

AF:

0.00113

AC:

137

Asia WGS

AF:

0.00116

AC:

AN:

3472

EpiCase

AF:

0.000218

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

LRRIQ3-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 28, 2019

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

0.19

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.43

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.010

T;T

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.72

MetaRNN

Benign

0.0058

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-2.6

D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.47

MVP

0.33

MPC

0.012

ClinPred

0.034

GERP RS

4.9

Varity_R

0.12

gMVP

0.030

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