NM_002309.5:c.*530G>T

Variant names:

• chr22-30243121-C-A
• rs737812
• NM_002309.5:c.*530G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333
• Publications: 14 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002309.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIF	NM_002309.5	MANE Select	c.*530G>T		3_prime_UTR	Exon 3 of 3	NP_002300.1
	LIF	NM_001257135.2		c.*693G>T		3_prime_UTR	Exon 2 of 2	NP_001244064.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIF	ENST00000249075.4	TSL:1 MANE Select	c.*530G>T		3_prime_UTR	Exon 3 of 3	ENSP00000249075.3

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44283 AN: 151966 Hom.: 6528 Cov.: 32

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.: 0 AF XY: 0.296 AC XY: 2368 AN XY: 8004

African (AFR) AF: 0.180 AC: 51 AN: 284

American (AMR) AF: 0.342 AC: 1014 AN: 2962

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 37 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: 63 AN: 274

Middle Eastern (MID) AF: 0.0455 AC: 1 AN: 22

European-Non Finnish (NFE) AF: 0.317 AC: 2355 AN: 7432

Other (OTH) AF: 0.283 AC: 176 AN: 622

GnomAD4 genome AF: 0.291 AC: 44299 AN: 152086 Hom.: 6532 Cov.: 32 AF XY: 0.288 AC XY: 21425 AN XY: 74354

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: 53 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22416 AN: 67974

Other (OTH) AF: 0.279 AC: 589 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.3
DANN	Benign	0.72
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs737812; hg19: chr22-30639110;