NM_001321122.2:c.-319-2316A>G

Variant names:

• chr3-46472782-T-C
• rs7641783
• NM_001321122.2:c.-319-2316A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321122.2(LTF):​c.-319-2316A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 151,970 control chromosomes in the GnomAD database, including 52,629 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 (52629 hom., cov: 29)
• Consequence: LTF NM_001321122.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• Publications: 9 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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 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.-319-2316A>G		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.-319-2316A>G		intron	N/A	ENSP00000397427.1
	LTF	ENST00000498301.1	TSL:4	c.-64-4463A>G		intron	N/A	ENSP00000508000.1

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125748 AN: 151852 Hom.: 52558 Cov.: 29

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.913

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.815

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

GnomAD4 genome AF: 0.828 AC: 125880 AN: 151970 Hom.: 52629 Cov.: 29 AF XY: 0.832 AC XY: 61796 AN XY: 74270

African (AFR) AF: 0.921 AC: 38182 AN: 41468

American (AMR) AF: 0.833 AC: 12728 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2729 AN: 3470

East Asian (EAS) AF: 0.991 AC: 5096 AN: 5142

South Asian (SAS) AF: 0.915 AC: 4400 AN: 4810

European-Finnish (FIN) AF: 0.802 AC: 8463 AN: 10550

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.759 AC: 51592 AN: 67944

Other (OTH) AF: 0.818 AC: 1720 AN: 2102

Alfa AF: 0.817 Hom.: 9468

Bravo AF: 0.834

Asia WGS AF: 0.944 AC: 3284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs7641783; hg19: chr3-46514272;