rs17141154

Positions:

• chr3-46449777-G-A

Variant summary

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

The NM_002343.6(LTF):​c.1057+77C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,499,612 control chromosomes in the GnomAD database, including 25,892 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 0.22 (4053 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21839 hom.)
• Consequence: LTF NM_002343.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.17

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTF	NM_002343.6	c.1057+77C>T		intron_variant		ENST00000231751.9
LTF	NM_001199149.2	c.925+77C>T		intron_variant
LTF	NM_001321121.2	c.1057+77C>T		intron_variant
LTF	NM_001321122.2	c.1018+77C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTF	ENST00000231751.9	c.1057+77C>T		intron_variant		1	NM_002343.6	P3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33063 AN: 151962 Hom.: 4039 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.175 AC: 235676 AN: 1347532 Hom.: 21839 AF XY: 0.177 AC XY: 119080 AN XY: 672176

Gnomad4 AFR exome AF: 0.339

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.269

Gnomad4 SAS exome AF: 0.264

Gnomad4 FIN exome AF: 0.189

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome AF: 0.218 AC: 33115 AN: 152080 Hom.: 4053 Cov.: 32 AF XY: 0.219 AC XY: 16266 AN XY: 74334

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.211

Alfa AF: 0.182 Hom.: 578

Bravo AF: 0.223

Asia WGS AF: 0.270 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.036
DANN	Benign	0.56

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: rs17141154; hg19: chr3-46491267; COSMIC: COSV51611977; COSMIC: COSV51611977;