3-46449777-G-A

Variant names:

• chr3-46449777-G-A
• rs17141154
• NM_002343.6:c.1057+77C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002343.6. 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_002343.6	MANE Select	c.1057+77C>T		intron	N/A	NP_002334.2
	LTF	NM_001321121.2		c.1057+77C>T		intron	N/A	NP_001308050.1
	LTF	NM_001321122.2		c.1018+77C>T		intron	N/A	NP_001308051.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTF	ENST00000231751.9	TSL:1 MANE Select	c.1057+77C>T		intron	N/A	ENSP00000231751.4
	LTF	ENST00000417439.5	TSL:1	c.1057+77C>T		intron	N/A	ENSP00000405546.1
	LTF	ENST00000443496.5	TSL:2	c.1018+77C>T		intron	N/A	ENSP00000397427.1

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

African (AFR) AF: 0.339 AC: 10383 AN: 30592

American (AMR) AF: 0.154 AC: 5830 AN: 37908

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 4152 AN: 24060

East Asian (EAS) AF: 0.269 AC: 10110 AN: 37566

South Asian (SAS) AF: 0.264 AC: 21128 AN: 80086

European-Finnish (FIN) AF: 0.189 AC: 9618 AN: 50888

Middle Eastern (MID) AF: 0.227 AC: 946 AN: 4176

European-Non Finnish (NFE) AF: 0.159 AC: 162770 AN: 1026024

Other (OTH) AF: 0.191 AC: 10739 AN: 56232

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

African (AFR) AF: 0.333 AC: 13809 AN: 41450

American (AMR) AF: 0.171 AC: 2619 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 576 AN: 3468

East Asian (EAS) AF: 0.290 AC: 1500 AN: 5174

South Asian (SAS) AF: 0.274 AC: 1323 AN: 4822

European-Finnish (FIN) AF: 0.182 AC: 1928 AN: 10566

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10733 AN: 67994

Other (OTH) AF: 0.211 AC: 446 AN: 2110

Alfa AF: 0.180 Hom.: 952

Bravo AF: 0.223

Asia WGS AF: 0.270 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.036
DANN	Benign	0.56
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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