rs929273

chr22-30244606-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIF	NM_002309.5	c.198+149C>T		intron_variant		ENST00000249075.4
LIF	NM_001257135.2	c.20-545C>T		intron_variant
LIF	XM_047441361.1	c.516+149C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIF	ENST00000249075.4	c.198+149C>T		intron_variant		1	NM_002309.5	P1
LIF	ENST00000403987.3	c.20-545C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38204 AN: 151890 Hom.: 5933 Cov.: 31

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

Gnomad4 AFR exome AF: 0.0591

Gnomad4 AMR exome AF: 0.409

Gnomad4 ASJ exome AF: 0.272

Gnomad4 EAS exome AF: 0.385

Gnomad4 SAS exome AF: 0.456

Gnomad4 FIN exome AF: 0.298

Gnomad4 NFE exome AF: 0.299

Gnomad4 OTH exome AF: 0.303

GnomAD4 genome AF: 0.251 AC: 38192 AN: 152010 Hom.: 5930 Cov.: 31 AF XY: 0.258 AC XY: 19211 AN XY: 74318

Gnomad4 AFR AF: 0.0657

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.276

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
Dann	Benign	0.30

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: rs929273; hg19: chr22-30640595;