rs737812

Positions:

• chr22-30243121-C-A
• chr22-30243121-C-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIF	NM_002309.5	c.*530G>T		3_prime_UTR_variant	3/3	ENST00000249075.4	NP_002300.1
LIF	NM_001257135.2	c.*693G>T		3_prime_UTR_variant	2/2		NP_001244064.1
LIF	XM_047441361.1	c.*530G>T		3_prime_UTR_variant	3/3		XP_047297317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIF	ENST00000249075	c.*530G>T		3_prime_UTR_variant	3/3	1	NM_002309.5	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

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.342

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.188

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.230

Gnomad4 NFE exome AF: 0.317

Gnomad4 OTH exome AF: 0.283

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

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.279

Alfa AF: 0.307 Hom.: 8015

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
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs737812; hg19: chr22-30639110;