chr3-46445350-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V482M) has been classified as Uncertain significance.

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

Publications

3 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 721972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LTF	NM_002343.6	MANE Select	c.1444G>T	p.Val482Leu	missense	Exon 12 of 17	NP_002334.2	P02788-1
LTF	NM_001321121.2		c.1438G>T	p.Val480Leu	missense	Exon 12 of 17	NP_001308050.1	E7ER44
LTF	NM_001321122.2		c.1405G>T	p.Val469Leu	missense	Exon 15 of 20	NP_001308051.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LTF	ENST00000231751.9	TSL:1 MANE Select	c.1444G>T	p.Val482Leu	missense	Exon 12 of 17	ENSP00000231751.4	P02788-1
LTF	ENST00000417439.5	TSL:1	c.1438G>T	p.Val480Leu	missense	Exon 12 of 17	ENSP00000405546.1	E7ER44
LTF	ENST00000947212.1		c.1444G>T	p.Val482Leu	missense	Exon 12 of 18	ENSP00000617271.1

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

GnomAD2 exomes

AF:

0.000988

AC:

248

AN:

251076

AF XY:

0.000862

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 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

African (AFR)

AF:

0.00514

AC:

172

AN:

33464

American (AMR)

AF:

0.00125

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00136

AC:

1515

AN:

1111758

Other (OTH)

AF:

0.00190

AC:

115

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

183

274

366

457

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00261

AC:

397

AN:

152350

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

189

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00623

AC:

259

AN:

41588

American (AMR)

AF:

0.00457

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000941

AC:

AN:

68028

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00139

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.80

M_CAP

Benign

0.0081

MetaRNN

Benign

0.0098

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

0.084

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.052

Sift

Benign

0.32

Sift4G

Benign

0.31

Polyphen

0.30

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

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over