NM_002343.6:c.1623C>T

Variant names:

• chr3-46443473-G-A
• rs1042073
• NM_002343.6:c.1623C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002343.6(LTF):​c.1623C>T​(p.Asn541Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,613,472 control chromosomes in the GnomAD database, including 94,300 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 (9806 hom., cov: 32)
  • Exomes 𝑓: 0.33 (84494 hom.)
• Consequence: LTF NM_002343.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.38
• Publications: 24 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP7: Synonymous conserved (PhyloP=-5.38 with no splicing effect.
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTF	NM_002343.6	MANE Select	c.1623C>T	p.Asn541Asn	synonymous	Exon 13 of 17	NP_002334.2	P02788-1
	LTF	NM_001321121.2		c.1617C>T	p.Asn539Asn	synonymous	Exon 13 of 17	NP_001308050.1	E7ER44
	LTF	NM_001321122.2		c.1584C>T	p.Asn528Asn	synonymous	Exon 16 of 20	NP_001308051.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTF	ENST00000231751.9	TSL:1 MANE Select	c.1623C>T	p.Asn541Asn	synonymous	Exon 13 of 17	ENSP00000231751.4	P02788-1
	LTF	ENST00000417439.5	TSL:1	c.1617C>T	p.Asn539Asn	synonymous	Exon 13 of 17	ENSP00000405546.1	E7ER44
	LTF	ENST00000947212.1		c.1656C>T	p.Asn552Asn	synonymous	Exon 14 of 18	ENSP00000617271.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53128 AN: 151940 Hom.: 9781 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.338

GnomAD2 exomes AF: 0.365 AC: 91759 AN: 251442 AF XY: 0.371

Gnomad AFR exome AF: 0.389

Gnomad AMR exome AF: 0.249

Gnomad ASJ exome AF: 0.359

Gnomad EAS exome AF: 0.676

Gnomad FIN exome AF: 0.388

Gnomad NFE exome AF: 0.302

Gnomad OTH exome AF: 0.349

GnomAD4 exome AF: 0.330 AC: 481951 AN: 1461414 Hom.: 84494 Cov.: 40 AF XY: 0.336 AC XY: 244058 AN XY: 727026

African (AFR) AF: 0.404 AC: 13518 AN: 33466

American (AMR) AF: 0.258 AC: 11554 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 9319 AN: 26134

East Asian (EAS) AF: 0.660 AC: 26198 AN: 39698

South Asian (SAS) AF: 0.520 AC: 44806 AN: 86238

European-Finnish (FIN) AF: 0.392 AC: 20920 AN: 53416

Middle Eastern (MID) AF: 0.414 AC: 2386 AN: 5762

European-Non Finnish (NFE) AF: 0.298 AC: 331813 AN: 1111600

Other (OTH) AF: 0.355 AC: 21437 AN: 60376

GnomAD4 genome AF: 0.350 AC: 53215 AN: 152058 Hom.: 9806 Cov.: 32 AF XY: 0.357 AC XY: 26568 AN XY: 74330

African (AFR) AF: 0.385 AC: 15977 AN: 41470

American (AMR) AF: 0.276 AC: 4220 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1233 AN: 3470

East Asian (EAS) AF: 0.670 AC: 3462 AN: 5164

South Asian (SAS) AF: 0.532 AC: 2564 AN: 4822

European-Finnish (FIN) AF: 0.391 AC: 4129 AN: 10548

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20502 AN: 67970

Other (OTH) AF: 0.345 AC: 729 AN: 2110

Alfa AF: 0.326 Hom.: 3776

Bravo AF: 0.341

Asia WGS AF: 0.577 AC: 2003 AN: 3478

EpiCase AF: 0.308

EpiControl AF: 0.300

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.087
DANN	Benign	0.58
PhyloP100		-5.4
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1042073; hg19: chr3-46484964; COSMIC: COSV51608438; COSMIC: COSV51608438;