rs6441992

Variant names:

• chr3-46443008-C-A
• rs6441992
• NM_002343.6:c.1655+433G>T

Variant summary

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

The NM_002343.6(LTF):​c.1655+433G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 152,020 control chromosomes in the GnomAD database, including 9,809 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 (9809 hom., cov: 32)
• Consequence: LTF NM_002343.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.616
• Publications: 4 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTF	NM_002343.6	c.1655+433G>T		intron_variant	Intron 13 of 16	ENST00000231751.9	NP_002334.2
LTF	NM_001321121.2	c.1649+433G>T		intron_variant	Intron 13 of 16		NP_001308050.1
LTF	NM_001321122.2	c.1616+433G>T		intron_variant	Intron 16 of 19		NP_001308051.1
LTF	NM_001199149.2	c.1523+433G>T		intron_variant	Intron 13 of 16		NP_001186078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTF	ENST00000231751.9	c.1655+433G>T		intron_variant	Intron 13 of 16	1	NM_002343.6	ENSP00000231751.4

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53142 AN: 151900 Hom.: 9783 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.350 AC: 53231 AN: 152020 Hom.: 9809 Cov.: 32 AF XY: 0.358 AC XY: 26565 AN XY: 74290

African (AFR) AF: 0.386 AC: 16006 AN: 41440

American (AMR) AF: 0.276 AC: 4216 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1233 AN: 3472

East Asian (EAS) AF: 0.670 AC: 3467 AN: 5172

South Asian (SAS) AF: 0.531 AC: 2559 AN: 4822

European-Finnish (FIN) AF: 0.392 AC: 4141 AN: 10562

Middle Eastern (MID) AF: 0.449 AC: 131 AN: 292

European-Non Finnish (NFE) AF: 0.301 AC: 20483 AN: 67960

Other (OTH) AF: 0.345 AC: 729 AN: 2110

Alfa AF: 0.350 Hom.: 2220

Bravo AF: 0.342

Asia WGS AF: 0.577 AC: 2004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.71
PhyloP100		0.62
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: rs6441992; hg19: chr3-46484499;