22-30244004-C-T

Position:

chr22-30244004-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002309.5(LIF):c.256G>A(p.Val86Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00661 in 1,613,556 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 40 hom. )

Consequence

LIF
NM_002309.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.663

Variant links:

Genes affected

LIF (HGNC:6596): (LIF interleukin 6 family cytokine) The protein encoded by this gene is a pleiotropic cytokine with roles in several different systems. It is involved in the induction of hematopoietic differentiation in normal and myeloid leukemia cells, induction of neuronal cell differentiation, regulator of mesenchymal to epithelial conversion during kidney development, and may also have a role in immune tolerance at the maternal-fetal interface. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

LIF links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006029725).

BP6

Variant 22-30244004-C-T is Benign according to our data. Variant chr22-30244004-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 403032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 778 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LIF	NM_002309.5 linkuse as main transcript	c.256G>A	p.Val86Met	missense_variant	3/3	ENST00000249075.4	NP_002300.1
LIF	NM_001257135.2 linkuse as main transcript	c.77G>A	p.Arg26His	missense_variant	2/2		NP_001244064.1
LIF	XM_047441361.1 linkuse as main transcript	c.574G>A	p.Val192Met	missense_variant	3/3		XP_047297317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIF	ENST00000249075.4 linkuse as main transcript	c.256G>A	p.Val86Met	missense_variant	3/3	1	NM_002309.5	ENSP00000249075	P1	P15018-1
LIF	ENST00000403987.3 linkuse as main transcript	c.77G>A	p.Arg26His	missense_variant	2/2	1		ENSP00000384450		P15018-2

Frequencies

GnomAD3 genomes

AF:

0.00512

AC:

779

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00759

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00521

AC:

1295

AN:

248444

Hom.:

AF XY:

0.00511

AC XY:

687

AN XY:

134450

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00335

Gnomad ASJ exome

AF:

0.0168

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00261

Gnomad FIN exome

AF:

0.00100

Gnomad NFE exome

AF:

0.00757

Gnomad OTH exome

AF:

0.00653

GnomAD4 exome

AF:

0.00677

AC:

9889

AN:

1461298

Hom.:

Cov.:

AF XY:

0.00666

AC XY:

4841

AN XY:

726916

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00351

Gnomad4 ASJ exome

AF:

0.0164

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00256

Gnomad4 FIN exome

AF:

0.00125

Gnomad4 NFE exome

AF:

0.00762

Gnomad4 OTH exome

AF:

0.00709

GnomAD4 genome

AF:

0.00511

AC:

778

AN:

152258

Hom.:

Cov.:

AF XY:

0.00506

AC XY:

377

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.00123

Gnomad4 NFE

AF:

0.00759

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00758

Hom.:

Bravo

AF:

0.00530

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.0102

AC:

ExAC

AF:

0.00518

AC:

629

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00900

EpiControl

AF:

0.00919

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	LIF: BP4, BS2 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.30

MetaRNN

Benign

0.0060

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

N;N

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.044

Vest4

0.17

MVP

0.32

ClinPred

0.0033

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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