Variant chr3-46439310-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.62

Variant links:

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]

LTF links:

LTF (HGNC:):

LTF links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTF	NM_002343.6 linkuse as main transcript	c.1894T>C	p.Leu632Leu	synonymous_variant	15/17	ENST00000231751.9	NP_002334.2	P02788-1V9HWI4
LTF	NM_001321121.2 linkuse as main transcript	c.1888T>C	p.Leu630Leu	synonymous_variant	15/17		NP_001308050.1	P02788Q2TUW9V9HWI4E7ER44
LTF	NM_001321122.2 linkuse as main transcript	c.1855T>C	p.Leu619Leu	synonymous_variant	18/20		NP_001308051.1	P02788V9HWI4B3KSL2
LTF	NM_001199149.2 linkuse as main transcript	c.1762T>C	p.Leu588Leu	synonymous_variant	15/17		NP_001186078.1	P02788-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTF	ENST00000231751.9 linkuse as main transcript	c.1894T>C	p.Leu632Leu	synonymous_variant	15/17	1	NM_002343.6	ENSP00000231751.4		P02788-1

Frequencies

GnomAD3 genomes

AF:

0.406

AC:

61713

AN:

151970

Hom.:

14069

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.391

AC:

97379

AN:

249018

Hom.:

21291

AF XY:

0.392

AC XY:

52701

AN XY:

134578

show subpopulations

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 SAS exome

AF:

0.570

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.:

AF XY:

0.333

AC XY:

242095

AN XY:

726054

show subpopulations

Gnomad4 AFR exome

AF:

0.600

Gnomad4 AMR exome

AF:

0.386

Gnomad4 ASJ exome

AF:

0.328

Gnomad4 EAS exome

AF:

0.686

Gnomad4 SAS exome

AF:

0.569

Gnomad4 FIN exome

AF:

0.375

Gnomad4 NFE exome

AF:

0.281

Gnomad4 OTH exome

AF:

0.349

GnomAD4 genome

AF:

0.406

AC:

61791

AN:

152088

Hom.:

14099

Cov.:

AF XY:

0.413

AC XY:

30706

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.588

Gnomad4 AMR

AF:

0.351

Gnomad4 ASJ

AF:

0.328

Gnomad4 EAS

AF:

0.660

Gnomad4 SAS

AF:

0.576

Gnomad4 FIN

AF:

0.379

Gnomad4 NFE

AF:

0.285

Gnomad4 OTH

AF:

0.395

Alfa

AF:

0.323

Hom.:

5338

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.8

DANN

Benign

0.50

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over