3-46445512-A-G

Position:

• chr3-46445512-A-G

Variant summary

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

The NM_002343.6(LTF):​c.1358-76T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,413,720 control chromosomes in the GnomAD database, including 82,478 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 0.35 (9911 hom., cov: 33)
  • Exomes 𝑓: 0.33 (72567 hom.)
• Consequence: LTF NM_002343.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.630

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTF	NM_002343.6	c.1358-76T>C		intron_variant		ENST00000231751.9
LTF	NM_001199149.2	c.1226-76T>C		intron_variant
LTF	NM_001321121.2	c.1352-76T>C		intron_variant
LTF	NM_001321122.2	c.1319-76T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTF	ENST00000231751.9	c.1358-76T>C		intron_variant		1	NM_002343.6	P3

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53386 AN: 152006 Hom.: 9885 Cov.: 33

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.339

GnomAD4 exome AF: 0.329 AC: 415493 AN: 1261596 Hom.: 72567 AF XY: 0.335 AC XY: 209487 AN XY: 624970

Gnomad4 AFR exome AF: 0.408

Gnomad4 AMR exome AF: 0.260

Gnomad4 ASJ exome AF: 0.355

Gnomad4 EAS exome AF: 0.656

Gnomad4 SAS exome AF: 0.519

Gnomad4 FIN exome AF: 0.392

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.354

GnomAD4 genome AF: 0.352 AC: 53474 AN: 152124 Hom.: 9911 Cov.: 33 AF XY: 0.359 AC XY: 26693 AN XY: 74348

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.347

Alfa AF: 0.214 Hom.: 474

Bravo AF: 0.343

Asia WGS AF: 0.578 AC: 2006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.67

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: rs2269435; hg19: chr3-46487003; COSMIC: COSV51607620; COSMIC: COSV51607620;