rs1475967

Positions:

• chr3-46448759-A-G
• chr3-46448759-A-T

Variant summary

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

The NM_002343.6(LTF):​c.1212+104T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 1,383,542 control chromosomes in the GnomAD database, including 108,728 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 0.51 (23728 hom., cov: 33)
  • Exomes 𝑓: 0.35 (85000 hom.)
• Consequence: LTF NM_002343.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.47

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTF	NM_002343.6	c.1212+104T>C		intron_variant		ENST00000231751.9	NP_002334.2
LTF	NM_001199149.2	c.1080+104T>C		intron_variant			NP_001186078.1
LTF	NM_001321121.2	c.1206+110T>C		intron_variant			NP_001308050.1
LTF	NM_001321122.2	c.1173+104T>C		intron_variant			NP_001308051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTF	ENST00000231751.9	c.1212+104T>C		intron_variant		1	NM_002343.6	ENSP00000231751	P3

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76925 AN: 152022 Hom.: 23660 Cov.: 33

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.448

GnomAD4 exome AF: 0.354 AC: 436252 AN: 1231402 Hom.: 85000 AF XY: 0.358 AC XY: 219267 AN XY: 611766

Gnomad4 AFR exome AF: 0.893

Gnomad4 AMR exome AF: 0.433

Gnomad4 ASJ exome AF: 0.369

Gnomad4 EAS exome AF: 0.603

Gnomad4 SAS exome AF: 0.524

Gnomad4 FIN exome AF: 0.401

Gnomad4 NFE exome AF: 0.311

Gnomad4 OTH exome AF: 0.392

GnomAD4 genome AF: 0.507 AC: 77060 AN: 152140 Hom.: 23728 Cov.: 33 AF XY: 0.511 AC XY: 38025 AN XY: 74384

Gnomad4 AFR AF: 0.866

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.454

Alfa AF: 0.276 Hom.: 754

Bravo AF: 0.522

Asia WGS AF: 0.583 AC: 2023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.34
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1475967; hg19: chr3-46490250;