Variant 1-110951401-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018372.4(LRIF1):c.1483G>A(p.Val495Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

LRIF1
NM_018372.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.145

Variant links:

Genes affected

LRIF1 (HGNC:30299): (ligand dependent nuclear receptor interacting factor 1) Predicted to enable retinoic acid receptor binding activity. Involved in dosage compensation by inactivation of X chromosome. Located in Barr body; centriolar satellite; and nucleoplasm. Colocalizes with chromosome, telomeric region. [provided by Alliance of Genome Resources, Apr 2022]

LRIF1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020358711).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LRIF1	NM_018372.4 linkuse as main transcript	c.1483G>A	p.Val495Ile	missense_variant	2/4	ENST00000369763.5
LRIF1	XM_005271029.5 linkuse as main transcript	c.1483G>A	p.Val495Ile	missense_variant	2/4
LRIF1	XM_017001769.3 linkuse as main transcript	c.1483G>A	p.Val495Ile	missense_variant	2/4
LRIF1	NM_001006945.2 linkuse as main transcript	c.-12-1278G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRIF1	ENST00000369763.5 linkuse as main transcript	c.1483G>A	p.Val495Ile	missense_variant	2/4	5	NM_018372.4	P1	Q5T3J3-1
	ENST00000440689.1 linkuse as main transcript	n.1695-783C>T		intron_variant, non_coding_transcript_variant		2
LRIF1	ENST00000485275.2 linkuse as main transcript	c.-12-1278G>A		intron_variant		2			Q5T3J3-2
LRIF1	ENST00000494675.5 linkuse as main transcript	c.-13+1131G>A		intron_variant		2			Q5T3J3-2

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000773

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000119

AC:

AN:

251302

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000390

AC:

AN:

1461828

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000250

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000356

Hom.:

Bravo

AF:

0.000280

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000988

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

Oct 05, 2023

The c.1483G>A (p.V495I) alteration is located in exon 2 (coding exon 2) of the LRIF1 gene. This alteration results from a G to A substitution at nucleotide position 1483, causing the valine (V) at amino acid position 495 to be replaced by an isoleucine (I). 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

0.089

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.024

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.34

M_CAP

Benign

0.0012

MetaRNN

Benign

0.020

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.20

REVEL

Benign

0.010

Sift

Benign

0.23

Sift4G

Benign

0.47

Polyphen

0.0030

Vest4

0.079

MVP

0.17

MPC

0.055

ClinPred

0.0061

GERP RS

-0.38

Varity_R

0.017

gMVP

0.085

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