dbSNP rs2269435: LTF:c.1358-76T>C (chr3-46445512-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002343.6(LTF):c.1358-76T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,413,720 control chromosomes in the GnomAD database, including 82,478 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 0.35 ( 9911 hom., cov: 33)

Exomes 𝑓: 0.33 ( 72567 hom. )

Consequence

LTF
NM_002343.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.630

Publications

5 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LTF	NM_002343.6 link	c.1358-76T>C	intron_variant	Intron 11 of 16	ENST00000231751.9	NP_002334.2	P02788-1V9HWI4
LTF	NM_001321121.2 link	c.1352-76T>C	intron_variant	Intron 11 of 16		NP_001308050.1	P02788Q2TUW9V9HWI4E7ER44
LTF	NM_001321122.2 link	c.1319-76T>C	intron_variant	Intron 14 of 19		NP_001308051.1	P02788V9HWI4B3KSL2
LTF	NM_001199149.2 link	c.1226-76T>C	intron_variant	Intron 11 of 16		NP_001186078.1	P02788-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTF	ENST00000231751.9 link	c.1358-76T>C		intron_variant	Intron 11 of 16	1	NM_002343.6	ENSP00000231751.4		P02788-1

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53386

AN:

152006

Hom.:

9885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.389

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.671

Gnomad SAS

AF:

0.531

Gnomad FIN

AF:

0.392

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.339

GnomAD4 exome

AF:

0.329

AC:

415493

AN:

1261596

Hom.:

72567

AF XY:

0.335

AC XY:

209487

AN XY:

624970

show subpopulations

African (AFR)

AF:

0.408

AC:

11569

AN:

28372

American (AMR)

AF:

0.260

AC:

9089

AN:

34896

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

7280

AN:

20526

East Asian (EAS)

AF:

0.656

AC:

23836

AN:

36326

South Asian (SAS)

AF:

0.519

AC:

36323

AN:

69952

European-Finnish (FIN)

AF:

0.392

AC:

18424

AN:

47016

Middle Eastern (MID)

AF:

0.414

AC:

2133

AN:

5156

European-Non Finnish (NFE)

AF:

0.298

AC:

288029

AN:

966284

Other (OTH)

AF:

0.354

AC:

18810

AN:

53068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

12694

25388

38083

50777

63471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9762

19524

29286

39048

48810

<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:

0.352

AC:

53474

AN:

152124

Hom.:

9911

Cov.:

AF XY:

0.359

AC XY:

26693

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.390

AC:

16176

AN:

41462

American (AMR)

AF:

0.277

AC:

4239

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

1231

AN:

3470

East Asian (EAS)

AF:

0.670

AC:

3466

AN:

5172

South Asian (SAS)

AF:

0.531

AC:

2565

AN:

4826

European-Finnish (FIN)

AF:

0.392

AC:

4150

AN:

10596

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.302

AC:

20514

AN:

67994

Other (OTH)

AF:

0.347

AC:

733

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1797

3594

5392

7189

8986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.214

Hom.:

474

Bravo

AF:

0.343

Asia WGS

AF:

0.578

AC:

2006

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.1

(source)

DANN

Benign

0.67

PhyloP100

-0.63

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over