rs6441991

Positions:

• chr3-46442792-T-A
• chr3-46442792-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002343.6(LTF):​c.1655+649A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 152,168 control chromosomes in the GnomAD database, including 419 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 0.061 (419 hom., cov: 32)
• Consequence: LTF NM_002343.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTF	NM_002343.6	c.1655+649A>T		intron_variant		ENST00000231751.9
LTF	NM_001199149.2	c.1523+649A>T		intron_variant
LTF	NM_001321121.2	c.1649+649A>T		intron_variant
LTF	NM_001321122.2	c.1616+649A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTF	ENST00000231751.9	c.1655+649A>T		intron_variant		1	NM_002343.6	P3

Frequencies

GnomAD3 genomes AF: 0.0611 AC: 9283 AN: 152050 Hom.: 422 Cov.: 32

Gnomad AFR AF: 0.0140

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0319

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.0734

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0760

Gnomad OTH AF: 0.0474

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

GnomAD4 genome AF: 0.0609 AC: 9273 AN: 152168 Hom.: 419 Cov.: 32 AF XY: 0.0666 AC XY: 4953 AN XY: 74370

Gnomad4 AFR AF: 0.0140

Gnomad4 AMR AF: 0.0318

Gnomad4 ASJ AF: 0.0366

Gnomad4 EAS AF: 0.0732

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.0760

Gnomad4 OTH AF: 0.0469

Alfa AF: 0.0390 Hom.: 35

Bravo AF: 0.0482

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.010
DANN	Benign	0.53

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

Other links and lift over

dbSNP: rs6441991; hg19: chr3-46484283;