NM_002343.6:c.1357+501C>T

Variant names:

• chr3-46445939-G-A
• rs2269438
• NM_002343.6:c.1357+501C>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.1357+501C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,048 control chromosomes in the GnomAD database, including 9,866 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 (9866 hom., cov: 32)
• Consequence: LTF NM_002343.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 2 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 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.1357+501C>T		intron	N/A	NP_002334.2
	LTF	NM_001321121.2		c.1351+501C>T		intron	N/A	NP_001308050.1
	LTF	NM_001321122.2		c.1318+501C>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.1357+501C>T		intron	N/A	ENSP00000231751.4
	LTF	ENST00000417439.5	TSL:1	c.1351+501C>T		intron	N/A	ENSP00000405546.1
	LTF	ENST00000443496.5	TSL:2	c.1318+501C>T		intron	N/A	ENSP00000397427.1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53316 AN: 151928 Hom.: 9840 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.351 AC: 53405 AN: 152048 Hom.: 9866 Cov.: 32 AF XY: 0.359 AC XY: 26644 AN XY: 74308

African (AFR) AF: 0.390 AC: 16175 AN: 41456

American (AMR) AF: 0.277 AC: 4241 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1229 AN: 3466

East Asian (EAS) AF: 0.670 AC: 3462 AN: 5166

South Asian (SAS) AF: 0.531 AC: 2562 AN: 4826

European-Finnish (FIN) AF: 0.389 AC: 4108 AN: 10556

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20495 AN: 67962

Other (OTH) AF: 0.347 AC: 733 AN: 2112

Alfa AF: 0.326 Hom.: 1366

Bravo AF: 0.343

Asia WGS AF: 0.578 AC: 2006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.14
DANN	Benign	0.38
PhyloP100		-1.4
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: rs2269438; hg19: chr3-46487430;