3-46465324-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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: Benign. The variant received -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.

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+2928T>C		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+2928T>C		intron	N/A	ENSP00000397427.1
	LTF	ENST00000498301.1	TSL:4	c.4+2928T>C		intron	N/A	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

African (AFR) AF: 0.948 AC: 39357 AN: 41530

American (AMR) AF: 0.835 AC: 12781 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 2731 AN: 3472

East Asian (EAS) AF: 0.996 AC: 5157 AN: 5178

South Asian (SAS) AF: 0.913 AC: 4401 AN: 4820

European-Finnish (FIN) AF: 0.801 AC: 8490 AN: 10602

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.754 AC: 51272 AN: 67978

Other (OTH) AF: 0.821 AC: 1735 AN: 2114

Alfa AF: 0.808 Hom.: 14512

Bravo AF: 0.841

Asia WGS AF: 0.950 AC: 3304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.013
DANN	Benign	0.63
PhyloP100		-2.3
PromoterAI		0.00090	Neutral

Splicing

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

Other links and lift over

dbSNP: rs4637321; hg19: chr3-46506814;