3-46439310-A-G

Variant names:

• chr3-46439310-A-G
• rs9110
• NM_002343.6:c.1894T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002343.6(LTF):​c.1894T>C​(p.Leu632Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,611,592 control chromosomes in the GnomAD database, including 100,459 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 0.41 (14099 hom., cov: 33)
  • Exomes 𝑓: 0.33 (86360 hom.)
• Consequence: LTF NM_002343.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62
• Publications: 25 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=1.62 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 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.1894T>C	p.Leu632Leu	synonymous	Exon 15 of 17	NP_002334.2
	LTF	NM_001321121.2		c.1888T>C	p.Leu630Leu	synonymous	Exon 15 of 17	NP_001308050.1
	LTF	NM_001321122.2		c.1855T>C	p.Leu619Leu	synonymous	Exon 18 of 20	NP_001308051.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTF	ENST00000231751.9	TSL:1 MANE Select	c.1894T>C	p.Leu632Leu	synonymous	Exon 15 of 17	ENSP00000231751.4
	LTF	ENST00000417439.5	TSL:1	c.1888T>C	p.Leu630Leu	synonymous	Exon 15 of 17	ENSP00000405546.1
	LTF	ENST00000443496.5	TSL:2	c.1855T>C	p.Leu619Leu	synonymous	Exon 18 of 20	ENSP00000397427.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61713 AN: 151970 Hom.: 14069 Cov.: 33

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.389

GnomAD2 exomes AF: 0.391 AC: 97379 AN: 249018 AF XY: 0.392

Gnomad AFR exome AF: 0.589

Gnomad AMR exome AF: 0.385

Gnomad ASJ exome AF: 0.331

Gnomad EAS exome AF: 0.645

Gnomad FIN exome AF: 0.372

Gnomad NFE exome AF: 0.286

Gnomad OTH exome AF: 0.349

GnomAD4 exome AF: 0.327 AC: 477270 AN: 1459504 Hom.: 86360 Cov.: 36 AF XY: 0.333 AC XY: 242095 AN XY: 726054

African (AFR) AF: 0.600 AC: 20027 AN: 33372

American (AMR) AF: 0.386 AC: 17113 AN: 44340

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 8509 AN: 25932

East Asian (EAS) AF: 0.686 AC: 27215 AN: 39684

South Asian (SAS) AF: 0.569 AC: 48900 AN: 85980

European-Finnish (FIN) AF: 0.375 AC: 20019 AN: 53364

Middle Eastern (MID) AF: 0.413 AC: 2373 AN: 5748

European-Non Finnish (NFE) AF: 0.281 AC: 312068 AN: 1110792

Other (OTH) AF: 0.349 AC: 21046 AN: 60292

GnomAD4 genome AF: 0.406 AC: 61791 AN: 152088 Hom.: 14099 Cov.: 33 AF XY: 0.413 AC XY: 30706 AN XY: 74338

African (AFR) AF: 0.588 AC: 24389 AN: 41488

American (AMR) AF: 0.351 AC: 5364 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1138 AN: 3468

East Asian (EAS) AF: 0.660 AC: 3408 AN: 5164

South Asian (SAS) AF: 0.576 AC: 2774 AN: 4818

European-Finnish (FIN) AF: 0.379 AC: 4011 AN: 10572

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19403 AN: 67976

Other (OTH) AF: 0.395 AC: 834 AN: 2110

Alfa AF: 0.319 Hom.: 6778

Bravo AF: 0.412

Asia WGS AF: 0.584 AC: 2028 AN: 3478

EpiCase AF: 0.289

EpiControl AF: 0.278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.8
DANN	Benign	0.50
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9110; hg19: chr3-46480801; COSMIC: COSV51606311;