Variant chr12-85055721-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000393217.7(LRRIQ1):c.928C>G(p.Gln310Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000186 in 1,603,996 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 2 hom. )

Consequence

LRRIQ1
ENST00000393217.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0570

Variant links:

Genes affected

LRRIQ1 (HGNC:25708): (leucine rich repeats and IQ motif containing 1)

LRRIQ1 links:

LRRIQ1 (HGNC:):

LRRIQ1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02203092).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRIQ1	NM_001079910.2 linkuse as main transcript	c.928C>G	p.Gln310Glu	missense_variant	8/27	ENST00000393217.7	NP_001073379.1	Q96JM4-4A0A140VJN5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRIQ1	ENST00000393217.7 linkuse as main transcript	c.928C>G	p.Gln310Glu	missense_variant	8/27	1	NM_001079910.2	ENSP00000376910.2		Q96JM4-4
LRRIQ1	ENST00000525971.6 linkuse as main transcript	n.1046C>G		non_coding_transcript_exon_variant	8/17	5

Frequencies

GnomAD3 genomes

AF:

0.000166

AC:

AN:

150376

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000975

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000341

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000181

AC:

AN:

242634

Hom.:

AF XY:

0.000145

AC XY:

AN XY:

131314

show subpopulations

Gnomad AFR exome

AF:

0.0000659

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.000361

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000188

AC:

273

AN:

1453504

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

136

AN XY:

722704

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.0000461

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.000226

Gnomad4 OTH exome

AF:

0.000117

GnomAD4 genome

AF:

0.000166

AC:

AN:

150492

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

73394

show subpopulations

Gnomad4 AFR

AF:

0.0000244

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000975

Gnomad4 NFE

AF:

0.000341

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000349

Hom.:

Bravo

AF:

0.000166

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.000214

AC:

EpiCase

AF:

0.000330

EpiControl

AF:

0.000239

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 14, 2023

The c.928C>G (p.Q310E) alteration is located in exon 8 (coding exon 7) of the LRRIQ1 gene. This alteration results from a C to G substitution at nucleotide position 928, causing the glutamine (Q) at amino acid position 310 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0028

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.73

M_CAP

Benign

0.021

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.3

REVEL

Benign

0.022

Sift

Benign

0.077

Sift4G

Benign

0.19

Polyphen

0.43

Vest4

0.23

MVP

0.46

MPC

0.017

ClinPred

0.041

GERP RS

3.4

Varity_R

0.12

gMVP

0.038

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