Variant 2-237764060-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001137552.2(LRRFIP1):c.2347C>G(p.His783Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,613,890 control chromosomes in the GnomAD database, including 58,563 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.29 ( 6816 hom., cov: 32)

Exomes 𝑓: 0.26 ( 51747 hom. )

Consequence

LRRFIP1
NM_001137552.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.953

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:

LRRFIP1 (HGNC:):

LRRFIP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.319268E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRFIP1	NM_001137550.2 linkuse as main transcript	c.1459+3855C>G		intron_variant		ENST00000308482.14	NP_001131022.1	Q32MZ4-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRFIP1	ENST00000308482.14 linkuse as main transcript	c.1459+3855C>G		intron_variant		1	NM_001137550.2	ENSP00000310109.9		Q32MZ4-4

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

44271

AN:

151926

Hom.:

6799

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.531

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.284

Gnomad MID

AF:

0.344

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.266

GnomAD3 exomes

AF:

0.294

AC:

73913

AN:

251226

Hom.:

11857

AF XY:

0.293

AC XY:

39830

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.364

Gnomad AMR exome

AF:

0.305

Gnomad ASJ exome

AF:

0.239

Gnomad EAS exome

AF:

0.522

Gnomad SAS exome

AF:

0.366

Gnomad FIN exome

AF:

0.272

Gnomad NFE exome

AF:

0.235

Gnomad OTH exome

AF:

0.274

GnomAD4 exome

AF:

0.257

AC:

375260

AN:

1461846

Hom.:

51747

Cov.:

AF XY:

0.260

AC XY:

188730

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.367

Gnomad4 AMR exome

AF:

0.305

Gnomad4 ASJ exome

AF:

0.241

Gnomad4 EAS exome

AF:

0.555

Gnomad4 SAS exome

AF:

0.363

Gnomad4 FIN exome

AF:

0.270

Gnomad4 NFE exome

AF:

0.231

Gnomad4 OTH exome

AF:

0.268

GnomAD4 genome

AF:

0.292

AC:

44330

AN:

152044

Hom.:

6816

Cov.:

AF XY:

0.300

AC XY:

22313

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.353

Gnomad4 AMR

AF:

0.308

Gnomad4 ASJ

AF:

0.233

Gnomad4 EAS

AF:

0.532

Gnomad4 SAS

AF:

0.359

Gnomad4 FIN

AF:

0.284

Gnomad4 NFE

AF:

0.234

Gnomad4 OTH

AF:

0.264

Alfa

AF:

0.252

Hom.:

3860

Bravo

AF:

0.293

TwinsUK

AF:

0.224

AC:

831

ALSPAC

AF:

0.228

AC:

880

ESP6500AA

AF:

0.371

AC:

1635

ESP6500EA

AF:

0.233

AC:

2004

ExAC

AF:

0.294

AC:

35743

Asia WGS

AF:

0.449

AC:

1559

AN:

3478

EpiCase

AF:

0.234

EpiControl

AF:

0.240

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.040

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.46

DEOGEN2

Benign

0.00013

.;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0060

LIST_S2

Benign

0.39

T;T;T

MetaRNN

Benign

0.000073

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.55

.;.;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.39

N;N;N

REVEL

Benign

0.083

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.039

MPC

0.092

ClinPred

0.0015

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.065

gMVP

0.012

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