3-46445350-C-A

Position:

chr3-46445350-C-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002343.6(LTF):c.1444G>T(p.Val482Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,613,862 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 0 hom. )

Consequence

LTF
NM_002343.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0840

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009766728).

BP6

Variant 3-46445350-C-A is Benign according to our data. Variant chr3-46445350-C-A is described in ClinVar as [Benign]. Clinvar id is 721972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LTF	NM_002343.6 linkuse as main transcript	c.1444G>T	p.Val482Leu	missense_variant	12/17	ENST00000231751.9	NP_002334.2
LTF	NM_001321121.2 linkuse as main transcript	c.1438G>T	p.Val480Leu	missense_variant	12/17		NP_001308050.1
LTF	NM_001321122.2 linkuse as main transcript	c.1405G>T	p.Val469Leu	missense_variant	15/20		NP_001308051.1
LTF	NM_001199149.2 linkuse as main transcript	c.1312G>T	p.Val438Leu	missense_variant	12/17		NP_001186078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTF	ENST00000231751.9 linkuse as main transcript	c.1444G>T	p.Val482Leu	missense_variant	12/17	1	NM_002343.6	ENSP00000231751	P3	P02788-1

Frequencies

GnomAD3 genomes

AF:

0.00258

AC:

393

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00615

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000941

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000988

AC:

248

AN:

251076

Hom.:

AF XY:

0.000862

AC XY:

117

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.00634

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000863

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00127

AC:

1862

AN:

1461512

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

888

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.00514

Gnomad4 AMR exome

AF:

0.00125

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.00136

Gnomad4 OTH exome

AF:

0.00190

GnomAD4 genome

AF:

0.00261

AC:

397

AN:

152350

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

189

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00623

Gnomad4 AMR

AF:

0.00457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000941

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000926

Hom.:

Bravo

AF:

0.00305

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000980

AC:

119

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;.;.;.

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.80

T;T;T;T

M_CAP

Benign

0.0081

MetaRNN

Benign

0.0098

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.;.;.

MutationTaster

Benign

0.69

D;D;D

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.4

N;N;N;N

REVEL

Benign

0.052

Sift

Benign

0.32

T;T;T;T

Sift4G

Benign

0.31

T;T;T;T

Polyphen

0.30

B;.;B;B

Vest4

0.23

MutPred

0.63

Gain of glycosylation at T480 (P = 0.0289);.;.;.;

MVP

0.40

MPC

0.093

ClinPred

0.058

GERP RS

2.2

Varity_R

0.35

gMVP

0.59

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over