chr3-46465324-A-G

Variant names:

• chr3-46465324-A-G
• rs4637321
• NM_001321122.2:c.4+2928T>C

Variant summary

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

The NM_001321122.2(LTF):​c.4+2928T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,196 control chromosomes in the GnomAD database, including 53,533 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 0.83 (53533 hom., cov: 32)
• Consequence: LTF NM_001321122.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTF	NM_001321122.2	c.4+2928T>C		intron_variant	Intron 4 of 19		NP_001308051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTF	ENST00000443496.5	c.4+2928T>C		intron_variant	Intron 4 of 19	2		ENSP00000397427.1
LTF	ENST00000498301.1	c.4+2928T>C		intron_variant	Intron 2 of 2	4		ENSP00000508000.1

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126746 AN: 152078 Hom.: 53461 Cov.: 32

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.912

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.818

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

GnomAD4 genome AF: 0.834 AC: 126881 AN: 152196 Hom.: 53533 Cov.: 32 AF XY: 0.838 AC XY: 62355 AN XY: 74408

Gnomad4 AFR AF: 0.948

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.787

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.913

Gnomad4 FIN AF: 0.801

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.821

Alfa AF: 0.798 Hom.: 6090

Bravo AF: 0.841

Asia WGS AF: 0.950 AC: 3304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.013
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4637321; hg19: chr3-46506814;