rs2269436

Positions:

• chr3-46445762-A-G

Variant summary

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

The NM_002343.6(LTF):​c.1358-326T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 152,256 control chromosomes in the GnomAD database, including 697 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 0.079 (697 hom., cov: 33)
• Consequence: LTF NM_002343.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTF	NM_002343.6	c.1358-326T>C		intron_variant		ENST00000231751.9
LTF	NM_001199149.2	c.1226-326T>C		intron_variant
LTF	NM_001321121.2	c.1352-326T>C		intron_variant
LTF	NM_001321122.2	c.1319-326T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTF	ENST00000231751.9	c.1358-326T>C		intron_variant		1	NM_002343.6	P3

Frequencies

GnomAD3 genomes AF: 0.0785 AC: 11950 AN: 152138 Hom.: 687 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0767

Gnomad ASJ AF: 0.0979

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.0989

Gnomad FIN AF: 0.0299

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0357

Gnomad OTH AF: 0.0718

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

GnomAD4 genome AF: 0.0787 AC: 11988 AN: 152256 Hom.: 697 Cov.: 33 AF XY: 0.0784 AC XY: 5838 AN XY: 74470

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0766

Gnomad4 ASJ AF: 0.0979

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.0990

Gnomad4 FIN AF: 0.0299

Gnomad4 NFE AF: 0.0357

Gnomad4 OTH AF: 0.0819

Alfa AF: 0.0561 Hom.: 46

Bravo AF: 0.0841

Asia WGS AF: 0.154 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.81

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: rs2269436; hg19: chr3-46487253;