3-46465599-C-CT

Variant names:

• chr3-46465599-C-CT
• rs5848800
• NM_001321122.2:c.4+2652dupA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001321122.2(LTF):​c.4+2652dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0042 (4 hom., cov: 0)
• Consequence: LTF NM_001321122.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873
• Publications: 2 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321122.2. 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
	LTF	NM_001321122.2		c.4+2652dupA		intron	N/A	NP_001308051.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTF	ENST00000443496.5	TSL:2	c.4+2652_4+2653insA		intron	N/A	ENSP00000397427.1
	LTF	ENST00000498301.1	TSL:4	c.4+2652_4+2653insA		intron	N/A	ENSP00000508000.1

Frequencies

GnomAD3 genomes AF: 0.00425 AC: 635 AN: 149448 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.00539

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00245

Gnomad ASJ AF: 0.0252

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.0111

Gnomad FIN AF: 0.00215

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00303

Gnomad OTH AF: 0.00244

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

GnomAD4 genome AF: 0.00423 AC: 633 AN: 149532 Hom.: 4 Cov.: 0 AF XY: 0.00428 AC XY: 312 AN XY: 72822

African (AFR) AF: 0.00536 AC: 218 AN: 40706

American (AMR) AF: 0.00245 AC: 37 AN: 15112

Ashkenazi Jewish (ASJ) AF: 0.0252 AC: 87 AN: 3454

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5130

South Asian (SAS) AF: 0.0111 AC: 53 AN: 4760

European-Finnish (FIN) AF: 0.00215 AC: 21 AN: 9772

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00303 AC: 204 AN: 67336

Other (OTH) AF: 0.00242 AC: 5 AN: 2066

Alfa AF: 0.00530 Hom.: 721

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5848800; hg19: chr3-46507089;