chr3-46465599-C-CT

Position:

• chr3-46465599-C-CT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001321122.2(LTF):​c.4+2652_4+2653insA 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

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTF	NM_001321122.2	c.4+2652_4+2653insA		intron_variant			NP_001308051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTF	ENST00000443496.5	c.4+2652_4+2653insA		intron_variant		2		ENSP00000397427
LTF	ENST00000498301.1	c.4+2652_4+2653insA		intron_variant		4		ENSP00000508000

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

Gnomad4 AFR AF: 0.00536

Gnomad4 AMR AF: 0.00245

Gnomad4 ASJ AF: 0.0252

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.0111

Gnomad4 FIN AF: 0.00215

Gnomad4 NFE AF: 0.00303

Gnomad4 OTH AF: 0.00242

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5848800; hg19: chr3-46507089;