Genetic Variant NM_002309.5:c.*1414A>C (chr22-30242237-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002309.5(LIF):c.*1414A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,200 control chromosomes in the GnomAD database, including 6,433 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 6405 hom., cov: 31)

Exomes 𝑓: 0.29 ( 28 hom. )

Consequence

LIF
NM_002309.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0570

Publications

32 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LIF	NM_002309.5 link	c.*1414A>C	3_prime_UTR_variant	Exon 3 of 3	ENST00000249075.4	NP_002300.1	P15018-1
LIF	NM_001257135.2 link	c.*1577A>C	3_prime_UTR_variant	Exon 2 of 2		NP_001244064.1	P15018-2
LIF	XM_047441361.1 link	c.*1414A>C	3_prime_UTR_variant	Exon 3 of 3		XP_047297317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIF	ENST00000249075.4 link	c.*1414A>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_002309.5	ENSP00000249075.3		P15018-1

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39767

AN:

151450

Hom.:

6409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0705

Gnomad AMI

AF:

0.254

Gnomad AMR

AF:

0.378

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.390

Gnomad SAS

AF:

0.458

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.292

GnomAD4 exome

AF:

0.291

AC:

184

AN:

632

Hom.:

Cov.:

AF XY:

0.269

AC XY:

113

AN XY:

420

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

AN:

East Asian (EAS)

AF:

0.344

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.322

AC:

112

AN:

348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.248

AC:

AN:

214

Other (OTH)

AF:

0.278

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.262

AC:

39753

AN:

151568

Hom.:

6405

Cov.:

AF XY:

0.269

AC XY:

19926

AN XY:

74070

show subpopulations

African (AFR)

AF:

0.0703

AC:

2901

AN:

41260

American (AMR)

AF:

0.379

AC:

5776

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

979

AN:

3464

East Asian (EAS)

AF:

0.390

AC:

1992

AN:

5112

South Asian (SAS)

AF:

0.457

AC:

2194

AN:

4806

European-Finnish (FIN)

AF:

0.309

AC:

3240

AN:

10502

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.320

AC:

21718

AN:

67862

Other (OTH)

AF:

0.289

AC:

610

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1395

2791

4186

5582

6977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.302

Hom.:

20541

Bravo

AF:

0.257

Asia WGS

AF:

0.375

AC:

1304

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.7

(source)

DANN

Benign

0.66

PhyloP100

-0.057

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over