3-46446997-G-A

Variant names:

• chr3-46446997-G-A
• rs743658
• NM_002343.6:c.1303+311C>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.1303+311C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0788 in 152,198 control chromosomes in the GnomAD database, including 699 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 0.079 (699 hom., cov: 32)
• Consequence: LTF NM_002343.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.32
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002343.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTF	NM_002343.6	MANE Select	c.1303+311C>T		intron	N/A	NP_002334.2
	LTF	NM_001321121.2		c.1297+311C>T		intron	N/A	NP_001308050.1
	LTF	NM_001321122.2		c.1264+311C>T		intron	N/A	NP_001308051.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTF	ENST00000231751.9	TSL:1 MANE Select	c.1303+311C>T		intron	N/A	ENSP00000231751.4
	LTF	ENST00000417439.5	TSL:1	c.1297+311C>T		intron	N/A	ENSP00000405546.1
	LTF	ENST00000947212.1		c.1303+311C>T		intron	N/A	ENSP00000617271.1

Frequencies

GnomAD3 genomes AF: 0.0786 AC: 11952 AN: 152080 Hom.: 689 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0765

Gnomad ASJ AF: 0.0979

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0301

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0358

Gnomad OTH AF: 0.0717

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

GnomAD4 genome AF: 0.0788 AC: 11990 AN: 152198 Hom.: 699 Cov.: 32 AF XY: 0.0785 AC XY: 5844 AN XY: 74414

African (AFR) AF: 0.150 AC: 6209 AN: 41488

American (AMR) AF: 0.0764 AC: 1169 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0979 AC: 340 AN: 3472

East Asian (EAS) AF: 0.148 AC: 766 AN: 5168

South Asian (SAS) AF: 0.102 AC: 493 AN: 4814

European-Finnish (FIN) AF: 0.0301 AC: 319 AN: 10614

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0358 AC: 2434 AN: 68024

Other (OTH) AF: 0.0818 AC: 173 AN: 2114

Alfa AF: 0.0578 Hom.: 44

Bravo AF: 0.0839

Asia WGS AF: 0.154 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0080
DANN	Benign	0.69
PhyloP100		-3.3
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: rs743658; hg19: chr3-46488488;