Variant rs11680012 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000392000.4(LRRFIP1):c.2069G>C(p.Arg690Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 1,614,196 control chromosomes in the GnomAD database, including 1,618 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.033 ( 103 hom., cov: 32)

Exomes 𝑓: 0.044 ( 1515 hom. )

Consequence

LRRFIP1
ENST00000392000.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.813

Variant links:

Genes affected

LRRFIP1 (HGNC:6702): (LRR binding FLII interacting protein 1) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and protein homodimerization activity. Involved in negative regulation of transcription by RNA polymerase II. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRFIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002564013).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRFIP1	NM_001137550.2 linkuse as main transcript	c.1459+3577G>C		intron_variant		ENST00000308482.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRFIP1	ENST00000308482.14 linkuse as main transcript	c.1459+3577G>C		intron_variant		1	NM_001137550.2	P1	Q32MZ4-4

Frequencies

GnomAD3 genomes

AF:

0.0332

AC:

5046

AN:

152212

Hom.:

103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00919

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0326

Gnomad ASJ

AF:

0.0415

Gnomad EAS

AF:

0.0583

Gnomad SAS

AF:

0.0388

Gnomad FIN

AF:

0.0277

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0453

Gnomad OTH

AF:

0.0440

GnomAD3 exomes

AF:

0.0389

AC:

9772

AN:

251000

Hom.:

237

AF XY:

0.0402

AC XY:

5449

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.00949

Gnomad AMR exome

AF:

0.0218

Gnomad ASJ exome

AF:

0.0414

Gnomad EAS exome

AF:

0.0625

Gnomad SAS exome

AF:

0.0410

Gnomad FIN exome

AF:

0.0285

Gnomad NFE exome

AF:

0.0455

Gnomad OTH exome

AF:

0.0422

GnomAD4 exome

AF:

0.0438

AC:

64042

AN:

1461866

Hom.:

1515

Cov.:

AF XY:

0.0439

AC XY:

31910

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00744

Gnomad4 AMR exome

AF:

0.0229

Gnomad4 ASJ exome

AF:

0.0423

Gnomad4 EAS exome

AF:

0.0478

Gnomad4 SAS exome

AF:

0.0398

Gnomad4 FIN exome

AF:

0.0280

Gnomad4 NFE exome

AF:

0.0466

Gnomad4 OTH exome

AF:

0.0432

GnomAD4 genome

AF:

0.0331

AC:

5043

AN:

152330

Hom.:

103

Cov.:

AF XY:

0.0327

AC XY:

2438

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00916

Gnomad4 AMR

AF:

0.0325

Gnomad4 ASJ

AF:

0.0415

Gnomad4 EAS

AF:

0.0580

Gnomad4 SAS

AF:

0.0384

Gnomad4 FIN

AF:

0.0277

Gnomad4 NFE

AF:

0.0453

Gnomad4 OTH

AF:

0.0435

Alfa

AF:

0.0429

Hom.:

Bravo

AF:

0.0317

TwinsUK

AF:

0.0469

AC:

174

ALSPAC

AF:

0.0483

AC:

186

ESP6500AA

AF:

0.0143

AC:

ESP6500EA

AF:

0.0445

AC:

383

ExAC

AF:

0.0387

AC:

4700

Asia WGS

AF:

0.0440

AC:

153

AN:

3478

EpiCase

AF:

0.0479

EpiControl

AF:

0.0536

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.77

Cadd

Benign

2.2

Dann

Benign

0.41

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.38

LIST_S2

Uncertain

0.87

D;D;D

MetaRNN

Benign

0.0026

T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

0.080

N;N;N

REVEL

Benign

0.056

Sift

Benign

0.082

T;T;T

Sift4G

Benign

0.47

T;T;T

Polyphen

0.063

B;B;B

Vest4

0.10

MPC

0.12

ClinPred

0.00045

GERP RS

-0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.031

gMVP

0.024

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over