Variant 3-46459723-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002343.6(LTF):c.140A>G(p.Lys47Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,575,478 control chromosomes in the GnomAD database, including 122,098 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.51 ( 23912 hom., cov: 31)

Exomes 𝑓: 0.35 ( 98186 hom. )

Consequence

LTF
NM_002343.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.40

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.6380334E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LTF	NM_002343.6 linkuse as main transcript	c.140A>G	p.Lys47Arg	missense_variant	2/17	ENST00000231751.9
LTF	NM_001321121.2 linkuse as main transcript	c.140A>G	p.Lys47Arg	missense_variant	2/17
LTF	NM_001321122.2 linkuse as main transcript	c.101A>G	p.Lys34Arg	missense_variant	5/20
LTF	NM_001199149.2 linkuse as main transcript	c.8A>G	p.Lys3Arg	missense_variant	2/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTF	ENST00000231751.9 linkuse as main transcript	c.140A>G	p.Lys47Arg	missense_variant	2/17	1	NM_002343.6	P3	P02788-1

Frequencies

GnomAD3 genomes

AF:

0.508

AC:

77114

AN:

151736

Hom.:

23848

Cov.:

show subpopulations

Gnomad AFR

AF:

0.866

Gnomad AMI

AF:

0.326

Gnomad AMR

AF:

0.453

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.680

Gnomad SAS

AF:

0.539

Gnomad FIN

AF:

0.400

Gnomad MID

AF:

0.474

Gnomad NFE

AF:

0.316

Gnomad OTH

AF:

0.456

GnomAD3 exomes

AF:

0.411

AC:

89929

AN:

218734

Hom.:

21109

AF XY:

0.404

AC XY:

48165

AN XY:

119306

show subpopulations

Gnomad AFR exome

AF:

0.871

Gnomad AMR exome

AF:

0.405

Gnomad ASJ exome

AF:

0.367

Gnomad EAS exome

AF:

0.668

Gnomad SAS exome

AF:

0.518

Gnomad FIN exome

AF:

0.395

Gnomad NFE exome

AF:

0.306

Gnomad OTH exome

AF:

0.371

GnomAD4 exome

AF:

0.354

AC:

503563

AN:

1423624

Hom.:

98186

Cov.:

AF XY:

0.357

AC XY:

252355

AN XY:

707444

show subpopulations

Gnomad4 AFR exome

AF:

0.892

Gnomad4 AMR exome

AF:

0.415

Gnomad4 ASJ exome

AF:

0.368

Gnomad4 EAS exome

AF:

0.658

Gnomad4 SAS exome

AF:

0.518

Gnomad4 FIN exome

AF:

0.401

Gnomad4 NFE exome

AF:

0.309

Gnomad4 OTH exome

AF:

0.398

GnomAD4 genome

AF:

0.509

AC:

77244

AN:

151854

Hom.:

23912

Cov.:

AF XY:

0.514

AC XY:

38123

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.866

Gnomad4 AMR

AF:

0.453

Gnomad4 ASJ

AF:

0.371

Gnomad4 EAS

AF:

0.678

Gnomad4 SAS

AF:

0.540

Gnomad4 FIN

AF:

0.400

Gnomad4 NFE

AF:

0.316

Gnomad4 OTH

AF:

0.462

Alfa

AF:

0.357

Hom.:

28507

Bravo

AF:

0.525

TwinsUK

AF:

0.308

AC:

1141

ALSPAC

AF:

0.318

AC:

1227

ESP6500AA

AF:

0.859

AC:

3783

ESP6500EA

AF:

0.316

AC:

2720

ExAC

AF:

0.436

AC:

52909

Asia WGS

AF:

0.617

AC:

2145

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.0060

DANN

Benign

0.73

DEOGEN2

Benign

0.071

T;.;.;.;.

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0086

LIST_S2

Benign

0.12

T;T;T;T;T

MetaRNN

Benign

8.6e-7

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.32

N;.;.;.;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.97

N;N;N;N;N

REVEL

Benign

0.016

Sift

Benign

0.40

T;T;T;T;T

Sift4G

Benign

0.41

T;T;T;T;T

Polyphen

0.0

B;.;B;B;.

Vest4

0.025

MPC

0.058

ClinPred

0.029

GERP RS

-9.7

Varity_R

0.092

gMVP

0.52

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

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