Variant 2-237708572-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000308482.14(LRRFIP1):c.125C>T(p.Ala42Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000239 in 1,590,712 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

LRRFIP1
ENST00000308482.14 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.29

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRFIP1	NM_001137550.2 linkuse as main transcript	c.125C>T	p.Ala42Val	missense_variant	2/24	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.125C>T	p.Ala42Val	missense_variant	2/24	1	NM_001137550.2	ENSP00000310109.9		Q32MZ4-4

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152272

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000218

AC:

AN:

229038

Hom.:

AF XY:

0.0000243

AC XY:

AN XY:

123686

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000516

Gnomad NFE exome

AF:

0.0000387

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000222

AC:

AN:

1438440

Hom.:

Cov.:

AF XY:

0.0000225

AC XY:

AN XY:

711950

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000242

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.0000255

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000165

AC:

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

May 24, 2023

The c.95C>T (p.A32V) alteration is located in exon 2 (coding exon 2) of the LRRFIP1 gene. This alteration results from a C to T substitution at nucleotide position 95, causing the alanine (A) at amino acid position 32 to be replaced by a valine (V). 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

Pathogenic

0.88

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

.;.;.;.;T

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.97

D;D;D;D;D

M_CAP

Benign

0.081

MetaRNN

Uncertain

0.48

T;T;T;T;T

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.3

.;M;M;.;M

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-3.3

D;D;D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0030

D;D;D;D;D

Sift4G

Uncertain

0.022

D;D;D;D;D

Polyphen

1.0

.;D;D;.;D

Vest4

0.77

MutPred

0.38

.;Loss of methylation at R34 (P = 0.1372);Loss of methylation at R34 (P = 0.1372);Loss of methylation at R34 (P = 0.1372);Loss of methylation at R34 (P = 0.1372);

MVP

0.72

MPC

0.41

ClinPred

0.87

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.28

gMVP

0.25

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