1-110951455-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018372.4(LRIF1):c.1429A>G(p.Ile477Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,614,000 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

LRIF1
NM_018372.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0260

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012562364).

BP6

Variant 1-110951455-T-C is Benign according to our data. Variant chr1-110951455-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2317165.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LRIF1	NM_018372.4 linkuse as main transcript	c.1429A>G	p.Ile477Val	missense_variant	2/4	ENST00000369763.5
LRIF1	XM_005271029.5 linkuse as main transcript	c.1429A>G	p.Ile477Val	missense_variant	2/4
LRIF1	XM_017001769.3 linkuse as main transcript	c.1429A>G	p.Ile477Val	missense_variant	2/4
LRIF1	NM_001006945.2 linkuse as main transcript	c.-12-1332A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRIF1	ENST00000369763.5 linkuse as main transcript	c.1429A>G	p.Ile477Val	missense_variant	2/4	5	NM_018372.4	P1	Q5T3J3-1
	ENST00000440689.1 linkuse as main transcript	n.1695-729T>C		intron_variant, non_coding_transcript_variant		2
LRIF1	ENST00000485275.2 linkuse as main transcript	c.-12-1332A>G		intron_variant		2			Q5T3J3-2
LRIF1	ENST00000494675.5 linkuse as main transcript	c.-13+1077A>G		intron_variant		2			Q5T3J3-2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000477

AC:

AN:

251354

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1461844

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000105

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000166

Hom.:

Bravo

AF:

0.000132

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.80

Cadd

Benign

2.4

Dann

Benign

0.65

DEOGEN2

Benign

0.017

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.50

M_CAP

Benign

0.0034

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.9

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

0.070

REVEL

Benign

0.034

Sift

Benign

1.0

Sift4G

Benign

0.55

Polyphen

0.0

Vest4

0.016

MVP

0.12

MPC

0.057

ClinPred

0.032

GERP RS

-0.21

Varity_R

0.013

gMVP

0.087

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