dbSNP rs929273: LIF:c.198+149C>T (chr22-30244606-G-A) – 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.198+149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 750,962 control chromosomes in the GnomAD database, including 38,021 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 0.25 ( 5930 hom., cov: 31)

Exomes 𝑓: 0.32 ( 32091 hom. )

Consequence

LIF
NM_002309.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.336

Publications

11 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=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LIF	NM_002309.5 link	c.198+149C>T	intron_variant	Intron 2 of 2	ENST00000249075.4	NP_002300.1	P15018-1
LIF	NM_001257135.2 link	c.20-545C>T	intron_variant	Intron 1 of 1		NP_001244064.1	P15018-2
LIF	XM_047441361.1 link	c.516+149C>T	intron_variant	Intron 2 of 2		XP_047297317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIF	ENST00000249075.4 link	c.198+149C>T		intron_variant	Intron 2 of 2	1	NM_002309.5	ENSP00000249075.3		P15018-1
LIF	ENST00000403987.3 link	c.20-545C>T		intron_variant	Intron 1 of 1	1		ENSP00000384450.3		P15018-2

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38204

AN:

151890

Hom.:

5933

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0659

Gnomad AMI

AF:

0.240

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.268

Gnomad EAS

AF:

0.388

Gnomad SAS

AF:

0.451

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.304

Gnomad OTH

AF:

0.279

GnomAD4 exome

AF:

0.317

AC:

189628

AN:

598952

Hom.:

32091

AF XY:

0.324

AC XY:

101704

AN XY:

313744

show subpopulations

African (AFR)

AF:

0.0591

AC:

964

AN:

16312

American (AMR)

AF:

0.409

AC:

12496

AN:

30562

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

4684

AN:

17216

East Asian (EAS)

AF:

0.385

AC:

12102

AN:

31468

South Asian (SAS)

AF:

0.456

AC:

25638

AN:

56214

European-Finnish (FIN)

AF:

0.298

AC:

11250

AN:

37804

Middle Eastern (MID)

AF:

0.329

AC:

800

AN:

2428

European-Non Finnish (NFE)

AF:

0.299

AC:

112237

AN:

375694

Other (OTH)

AF:

0.303

AC:

9457

AN:

31254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

6501

13003

19504

26006

32507

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1616

3232

4848

6464

8080

<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:

0.251

AC:

38192

AN:

152010

Hom.:

5930

Cov.:

AF XY:

0.258

AC XY:

19211

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.0657

AC:

2725

AN:

41482

American (AMR)

AF:

0.364

AC:

5554

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.268

AC:

928

AN:

3462

East Asian (EAS)

AF:

0.388

AC:

1996

AN:

5146

South Asian (SAS)

AF:

0.450

AC:

2170

AN:

4818

European-Finnish (FIN)

AF:

0.306

AC:

3234

AN:

10582

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.304

AC:

20675

AN:

67932

Other (OTH)

AF:

0.276

AC:

583

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1381

2763

4144

5526

6907

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<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:

0.267

Hom.:

764

Bravo

AF:

0.245

Asia WGS

AF:

0.373

AC:

1298

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.8

(source)

DANN

Benign

0.30

PhyloP100

-0.34

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