dbSNP rs737812: LIF:c.*530G>T (chr22-30243121-C-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.*530G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 167,264 control chromosomes in the GnomAD database, including 7,310 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 0.29 ( 6532 hom., cov: 32)

Exomes 𝑓: 0.30 ( 778 hom. )

Consequence

LIF
NM_002309.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.333

Publications

14 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=-0.79).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LIF	NM_002309.5 link	c.*530G>T	3_prime_UTR_variant	Exon 3 of 3	ENST00000249075.4	NP_002300.1	P15018-1
LIF	NM_001257135.2 link	c.*693G>T	3_prime_UTR_variant	Exon 2 of 2		NP_001244064.1	P15018-2
LIF	XM_047441361.1 link	c.*530G>T	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.*530G>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_002309.5	ENSP00000249075.3		P15018-1

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

44283

AN:

151966

Hom.:

6528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.396

Gnomad AMR

AF:

0.312

Gnomad ASJ

AF:

0.289

Gnomad EAS

AF:

0.211

Gnomad SAS

AF:

0.304

Gnomad FIN

AF:

0.263

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.330

Gnomad OTH

AF:

0.282

GnomAD4 exome

AF:

0.299

AC:

4545

AN:

15178

Hom.:

778

Cov.:

AF XY:

0.296

AC XY:

2368

AN XY:

8004

show subpopulations

African (AFR)

AF:

0.180

AC:

AN:

284

American (AMR)

AF:

0.342

AC:

1014

AN:

2962

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

AN:

160

East Asian (EAS)

AF:

0.188

AC:

248

AN:

1322

South Asian (SAS)

AF:

0.286

AC:

600

AN:

2100

European-Finnish (FIN)

AF:

0.230

AC:

AN:

274

Middle Eastern (MID)

AF:

0.0455

AC:

AN:

European-Non Finnish (NFE)

AF:

0.317

AC:

2355

AN:

7432

Other (OTH)

AF:

0.283

AC:

176

AN:

622

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

149

299

448

598

747

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<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:

0.291

AC:

44299

AN:

152086

Hom.:

6532

Cov.:

AF XY:

0.288

AC XY:

21425

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.236

AC:

9768

AN:

41474

American (AMR)

AF:

0.312

AC:

4765

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.289

AC:

1005

AN:

3472

East Asian (EAS)

AF:

0.211

AC:

1093

AN:

5172

South Asian (SAS)

AF:

0.306

AC:

1472

AN:

4818

European-Finnish (FIN)

AF:

0.263

AC:

2778

AN:

10578

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.330

AC:

22416

AN:

67974

Other (OTH)

AF:

0.279

AC:

589

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1615

3229

4844

6458

8073

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.310

Hom.:

12013

Bravo

AF:

0.294

Asia WGS

AF:

0.255

AC:

889

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.3

(source)

DANN

Benign

0.72

PhyloP100

0.33

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