rs2269438

chr3-46445939-G-A

Variant summary

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

The NM_002343.6(LTF):c.1357+501C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,048 control chromosomes in the GnomAD database, including 9,866 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 0.35 (9866 hom., cov: 32)
• Consequence: LTF NM_002343.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

Genes affected

LTF (HGNC:6720): (lactotransferrin) This gene is a member of the transferrin family of genes and its protein product is found in the secondary granules of neutrophils. The protein is a major iron-binding protein in milk and body secretions with an antimicrobial activity, making it an important component of the non-specific immune system. The protein demonstrates a broad spectrum of properties, including regulation of iron homeostasis, host defense against a broad range of microbial infections, anti-inflammatory activity, regulation of cellular growth and differentiation and protection against cancer development and metastasis. Antimicrobial, antiviral, antifungal and antiparasitic activity has been found for this protein and its peptides. Activity against both DNA and RNA viruses has been found, including activity against SARS-CoV-2, and HIV. [provided by RefSeq, Jul 2021]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTF	NM_002343.6	c.1357+501C>T		intron_variant		ENST00000231751.9
LTF	NM_001199149.2	c.1225+501C>T		intron_variant
LTF	NM_001321121.2	c.1351+501C>T		intron_variant
LTF	NM_001321122.2	c.1318+501C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTF	ENST00000231751.9	c.1357+501C>T		intron_variant		1	NM_002343.6	P3

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53316 AN: 151928 Hom.: 9840 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.339

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.351 AC: 53405 AN: 152048 Hom.: 9866 Cov.: 32 AF XY: 0.359 AC XY: 26644 AN XY: 74308

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.347

Alfa AF: 0.326 Hom.: 1366

Bravo AF: 0.343

Asia WGS AF: 0.578 AC: 2006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.14
Dann	Benign	0.38

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: rs2269438; hg19: chr3-46487430;