rs2269436

Variant names:

• chr3-46445762-A-G
• rs2269436
• NM_002343.6:c.1358-326T>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.1358-326T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 152,256 control chromosomes in the GnomAD database, including 697 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 (697 hom., cov: 33)
• Consequence: LTF NM_002343.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTF	NM_002343.6	c.1358-326T>C		intron_variant	Intron 11 of 16	ENST00000231751.9	NP_002334.2
LTF	NM_001321121.2	c.1352-326T>C		intron_variant	Intron 11 of 16		NP_001308050.1
LTF	NM_001321122.2	c.1319-326T>C		intron_variant	Intron 14 of 19		NP_001308051.1
LTF	NM_001199149.2	c.1226-326T>C		intron_variant	Intron 11 of 16		NP_001186078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTF	ENST00000231751.9	c.1358-326T>C		intron_variant	Intron 11 of 16	1	NM_002343.6	ENSP00000231751.4

Frequencies

GnomAD3 genomes AF: 0.0785 AC: 11950 AN: 152138 Hom.: 687 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0767

Gnomad ASJ AF: 0.0979

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.0989

Gnomad FIN AF: 0.0299

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0357

Gnomad OTH AF: 0.0718

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

GnomAD4 genome AF: 0.0787 AC: 11988 AN: 152256 Hom.: 697 Cov.: 33 AF XY: 0.0784 AC XY: 5838 AN XY: 74470

African (AFR) AF: 0.150 AC: 6219 AN: 41514

American (AMR) AF: 0.0766 AC: 1173 AN: 15304

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

East Asian (EAS) AF: 0.148 AC: 770 AN: 5192

South Asian (SAS) AF: 0.0990 AC: 477 AN: 4820

European-Finnish (FIN) AF: 0.0299 AC: 318 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0357 AC: 2431 AN: 68012

Other (OTH) AF: 0.0819 AC: 173 AN: 2112

Alfa AF: 0.0561 Hom.: 46

Bravo AF: 0.0841

Asia WGS AF: 0.154 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.81
PhyloP100		0.073
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: rs2269436; hg19: chr3-46487253;