NM_002343.6:c.208-1284G>A

Variant names:

• chr3-46457682-C-T
• rs7629657
• NM_002343.6:c.208-1284G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002343.6(LTF):​c.208-1284G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,254 control chromosomes in the GnomAD database, including 1,305 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 0.12 (1305 hom., cov: 33)
• Consequence: LTF NM_002343.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 6 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTF	NM_002343.6	c.208-1284G>A		intron_variant	Intron 2 of 16	ENST00000231751.9	NP_002334.2
LTF	NM_001321121.2	c.208-1284G>A		intron_variant	Intron 2 of 16		NP_001308050.1
LTF	NM_001321122.2	c.169-1284G>A		intron_variant	Intron 5 of 19		NP_001308051.1
LTF	NM_001199149.2	c.76-1284G>A		intron_variant	Intron 2 of 16		NP_001186078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTF	ENST00000231751.9	c.208-1284G>A		intron_variant	Intron 2 of 16	1	NM_002343.6	ENSP00000231751.4

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18130 AN: 152136 Hom.: 1295 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0650

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0804

Gnomad OTH AF: 0.108

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.119 AC: 18177 AN: 152254 Hom.: 1305 Cov.: 33 AF XY: 0.121 AC XY: 8976 AN XY: 74464

African (AFR) AF: 0.159 AC: 6605 AN: 41516

American (AMR) AF: 0.208 AC: 3187 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 544 AN: 3468

East Asian (EAS) AF: 0.151 AC: 786 AN: 5190

South Asian (SAS) AF: 0.105 AC: 508 AN: 4826

European-Finnish (FIN) AF: 0.0650 AC: 689 AN: 10606

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0804 AC: 5473 AN: 68032

Other (OTH) AF: 0.118 AC: 249 AN: 2114

Alfa AF: 0.116 Hom.: 187

Bravo AF: 0.127

Asia WGS AF: 0.167 AC: 578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.3
DANN	Benign	0.82
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7629657; hg19: chr3-46499172;