rs4683235

Positions:

• chr3-46460441-C-T

Variant summary

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

The NM_002343.6(LTF):​c.44-622G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 403,422 control chromosomes in the GnomAD database, including 3,053 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 0.12 (1295 hom., cov: 33)
  • Exomes 𝑓: 0.11 (1758 hom.)
• Consequence: LTF NM_002343.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTF	NM_002343.6	c.44-622G>A		intron_variant		ENST00000231751.9	NP_002334.2
LTF	NM_001199149.2	c.-89-622G>A		intron_variant			NP_001186078.1
LTF	NM_001321121.2	c.44-622G>A		intron_variant			NP_001308050.1
LTF	NM_001321122.2	c.5-622G>A		intron_variant			NP_001308051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTF	ENST00000231751.9	c.44-622G>A		intron_variant		1	NM_002343.6	ENSP00000231751	P3

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18101 AN: 152122 Hom.: 1285 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0803

Gnomad OTH AF: 0.108

GnomAD4 exome AF: 0.106 AC: 26613 AN: 251182 Hom.: 1758 AF XY: 0.103 AC XY: 14494 AN XY: 140954

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.0691

Gnomad4 NFE exome AF: 0.0810

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.119 AC: 18148 AN: 152240 Hom.: 1295 Cov.: 33 AF XY: 0.120 AC XY: 8961 AN XY: 74434

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.0649

Gnomad4 NFE AF: 0.0803

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0892 Hom.: 1392

Bravo AF: 0.127

Asia WGS AF: 0.166 AC: 577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.057
DANN	Benign	0.41

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: rs4683235; hg19: chr3-46501931; COSMIC: COSV51606616; COSMIC: COSV51606616;