Variant 3-37055106-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006309.4(LRRFIP2):c.1930A>G(p.Ile644Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000119 in 1,595,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

LRRFIP2
NM_006309.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.12

Variant links:

Genes affected

LRRFIP2 (HGNC:6703): (LRR binding FLII interacting protein 2) The protein encoded by this gene, along with MYD88, binds to the cytosolic tail of toll-like receptor 4 (TLR4), which results in activation of nuclear factor kappa B signaling. The ubiquitin-like protein FAT10 prevents the interaction of the encoded protein and TLR4, thereby inactivating the nuclear factor kappa B signaling pathway. In addition, this protein can downregulate the NLRP3 inflammasome by recruiting the caspase-1 inhibitor Flightless-I to the inflammasome complex. [provided by RefSeq, Jan 2017]

LRRFIP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2659251).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRFIP2	NM_006309.4 linkuse as main transcript	c.1930A>G	p.Ile644Val	missense_variant	26/28	ENST00000336686.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRFIP2	ENST00000336686.9 linkuse as main transcript	c.1930A>G	p.Ile644Val	missense_variant	26/28	1	NM_006309.4		Q9Y608-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000426

AC:

AN:

234854

Hom.:

AF XY:

0.00

AC XY:

AN XY:

127828

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:

0.00

Gnomad NFE exome

AF:

0.00000919

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000125

AC:

AN:

1443288

Hom.:

Cov.:

AF XY:

0.00000974

AC XY:

AN XY:

718508

show subpopulations

Gnomad4 AFR exome

AF:

0.0000311

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000154

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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 27, 2022

The c.1930A>G (p.I644V) alteration is located in exon 27 (coding exon 25) of the LRRFIP2 gene. This alteration results from a A to G substitution at nucleotide position 1930, causing the isoleucine (I) at amino acid position 644 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

Benign

0.099

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Benign

-0.31

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D;.;D;D

M_CAP

Benign

0.0063

MetaRNN

Benign

0.27

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.59

N;N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.21

T;T;T;T;T

Sift4G

Benign

0.44

T;T;T;T;T

Polyphen

0.12

B;B;B;.;B

Vest4

0.44

MutPred

0.60

.;Loss of ubiquitination at K639 (P = 0.1435);.;.;.;

MVP

0.43

ClinPred

0.55

GERP RS

5.7

Varity_R

0.098

gMVP

0.15

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