NM_001321122.2:c.-64-400G>A

Variant names:

• chr3-46468719-C-T
• rs1520483
• NM_001321122.2:c.-64-400G>A

Variant summary

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

The NM_001321122.2(LTF):​c.-64-400G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,166 control chromosomes in the GnomAD database, including 8,971 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 0.31 (8971 hom., cov: 33)
• Consequence: LTF NM_001321122.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346
• Publications: 15 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.492 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.-64-400G>A		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.-64-400G>A		intron	N/A	ENSP00000397427.1
	LTF	ENST00000498301.1	TSL:4	c.-64-400G>A		intron	N/A	ENSP00000508000.1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47291 AN: 152048 Hom.: 8966 Cov.: 33

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.311 AC: 47301 AN: 152166 Hom.: 8971 Cov.: 33 AF XY: 0.315 AC XY: 23452 AN XY: 74402

African (AFR) AF: 0.0846 AC: 3517 AN: 41550

American (AMR) AF: 0.343 AC: 5240 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1649 AN: 3470

East Asian (EAS) AF: 0.508 AC: 2629 AN: 5178

South Asian (SAS) AF: 0.416 AC: 2003 AN: 4820

European-Finnish (FIN) AF: 0.428 AC: 4522 AN: 10576

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26660 AN: 67972

Other (OTH) AF: 0.308 AC: 651 AN: 2114

Alfa AF: 0.344 Hom.: 2153

Bravo AF: 0.297

Asia WGS AF: 0.429 AC: 1492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.35
PhyloP100		-0.35

Splicing

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

Other links and lift over

dbSNP: rs1520483; hg19: chr3-46510209;