rs9862388

Variant names:

• chr3-46462826-A-G
• rs9862388
• NM_002343.6:c.43+1999T>C

Variant summary

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

The NM_002343.6(LTF):​c.43+1999T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,880 control chromosomes in the GnomAD database, including 23,563 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 0.50 (23563 hom., cov: 31)
• Consequence: LTF NM_002343.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 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.43+1999T>C		intron	N/A	NP_002334.2
	LTF	NM_001321121.2		c.43+1999T>C		intron	N/A	NP_001308050.1
	LTF	NM_001321122.2		c.5-3007T>C		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.43+1999T>C		intron	N/A	ENSP00000231751.4
	LTF	ENST00000417439.5	TSL:1	c.43+1999T>C		intron	N/A	ENSP00000405546.1
	LTF	ENST00000443496.5	TSL:2	c.5-3007T>C		intron	N/A	ENSP00000397427.1

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76361 AN: 151762 Hom.: 23491 Cov.: 31

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.504 AC: 76502 AN: 151880 Hom.: 23563 Cov.: 31 AF XY: 0.508 AC XY: 37703 AN XY: 74246

African (AFR) AF: 0.872 AC: 36097 AN: 41418

American (AMR) AF: 0.452 AC: 6894 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1289 AN: 3470

East Asian (EAS) AF: 0.513 AC: 2647 AN: 5158

South Asian (SAS) AF: 0.530 AC: 2550 AN: 4812

European-Finnish (FIN) AF: 0.400 AC: 4219 AN: 10542

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21423 AN: 67904

Other (OTH) AF: 0.452 AC: 951 AN: 2104

Alfa AF: 0.428 Hom.: 2825

Bravo AF: 0.520

Asia WGS AF: 0.550 AC: 1910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.52
PhyloP100		-0.23
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: rs9862388; hg19: chr3-46504316;