Genetic Variant NM_002343.6:c.1057+77C>T (chr3-46449777-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002343.6(LTF):c.1057+77C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,499,612 control chromosomes in the GnomAD database, including 25,892 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 0.22 ( 4053 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21839 hom. )

Consequence

LTF
NM_002343.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.17

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 (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LTF	NM_002343.6 link	c.1057+77C>T	intron_variant	Intron 8 of 16	ENST00000231751.9	NP_002334.2	P02788-1V9HWI4
LTF	NM_001321121.2 link	c.1057+77C>T	intron_variant	Intron 8 of 16		NP_001308050.1	P02788Q2TUW9V9HWI4E7ER44
LTF	NM_001321122.2 link	c.1018+77C>T	intron_variant	Intron 11 of 19		NP_001308051.1	P02788V9HWI4B3KSL2
LTF	NM_001199149.2 link	c.925+77C>T	intron_variant	Intron 8 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.1057+77C>T		intron_variant	Intron 8 of 16	1	NM_002343.6	ENSP00000231751.4		P02788-1

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33063

AN:

151962

Hom.:

4039

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.290

Gnomad SAS

AF:

0.274

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.158

Gnomad OTH

AF:

0.214

GnomAD4 exome

AF:

0.175

AC:

235676

AN:

1347532

Hom.:

21839

AF XY:

0.177

AC XY:

119080

AN XY:

672176

show subpopulations

Gnomad4 AFR exome

AF:

0.339

Gnomad4 AMR exome

AF:

0.154

Gnomad4 ASJ exome

AF:

0.173

Gnomad4 EAS exome

AF:

0.269

Gnomad4 SAS exome

AF:

0.264

Gnomad4 FIN exome

AF:

0.189

Gnomad4 NFE exome

AF:

0.159

Gnomad4 OTH exome

AF:

0.191

GnomAD4 genome

AF:

0.218

AC:

33115

AN:

152080

Hom.:

4053

Cov.:

AF XY:

0.219

AC XY:

16266

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.333

Gnomad4 AMR

AF:

0.171

Gnomad4 ASJ

AF:

0.166

Gnomad4 EAS

AF:

0.290

Gnomad4 SAS

AF:

0.274

Gnomad4 FIN

AF:

0.182

Gnomad4 NFE

AF:

0.158

Gnomad4 OTH

AF:

0.211

Alfa

AF:

0.182

Hom.:

578

Bravo

AF:

0.223

Asia WGS

AF:

0.270

AC:

936

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.036

DANN

Benign

0.56

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