Variant 1-74041739-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001105659.2(LRRIQ3):c.1192A>G(p.Ile398Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00487 in 1,613,678 control chromosomes in the GnomAD database, including 341 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.027 ( 182 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 159 hom. )

Consequence

LRRIQ3
NM_001105659.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.952

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020168126).

BP6

Variant 1-74041739-T-C is Benign according to our data. Variant chr1-74041739-T-C is described in ClinVar as [Benign]. Clinvar id is 775562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRIQ3	NM_001105659.2 linkuse as main transcript	c.1192A>G	p.Ile398Val	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.1192A>G	p.Ile398Val	missense_variant	7/8	5	NM_001105659.2	P2	A6PVS8-1
LRRIQ3	ENST00000395089.5 linkuse as main transcript	c.1192A>G	p.Ile398Val	missense_variant	6/7	5		P2	A6PVS8-1
LRRIQ3	ENST00000417067.5 linkuse as main transcript	c.131-14770A>G		intron_variant		2
LRRIQ3	ENST00000415760.5 linkuse as main transcript	c.*2655A>G		3_prime_UTR_variant, NMD_transcript_variant	9/10	2			A6PVS8-2

Frequencies

GnomAD3 genomes

AF:

0.0265

AC:

4033

AN:

152078

Hom.:

183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0926

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00892

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00631

AC:

1571

AN:

248958

Hom.:

AF XY:

0.00461

AC XY:

623

AN XY:

135080

show subpopulations

Gnomad AFR exome

AF:

0.0919

Gnomad AMR exome

AF:

0.00290

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000221

Gnomad OTH exome

AF:

0.00248

GnomAD4 exome

AF:

0.00261

AC:

3813

AN:

1461482

Hom.:

159

Cov.:

AF XY:

0.00218

AC XY:

1583

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.0941

Gnomad4 AMR exome

AF:

0.00387

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000854

Gnomad4 OTH exome

AF:

0.00571

GnomAD4 genome

AF:

0.0266

AC:

4046

AN:

152196

Hom.:

182

Cov.:

AF XY:

0.0253

AC XY:

1883

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0926

Gnomad4 AMR

AF:

0.00884

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.00489

Hom.:

Bravo

AF:

0.0298

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0921

AC:

339

ESP6500EA

AF:

0.000978

AC:

ExAC

AF:

0.00780

AC:

942

Asia WGS

AF:

0.00636

AC:

AN:

3476

EpiCase

AF:

0.000273

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

LRRIQ3-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 01, 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). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.88

Cadd

Benign

0.053

Dann

Benign

0.22

DEOGEN2

Benign

0.00032

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.032

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.25

N;N

REVEL

Benign

0.010

Sift

Benign

0.16

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0020

B;B

Vest4

0.022

MVP

0.030

MPC

0.0044

ClinPred

0.0049

GERP RS

-3.7

Varity_R

0.028

gMVP

0.012

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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