rs1042073

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-46443473-G-A
• chr3-46443473-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTF	NM_002343.6	c.1623C>T	p.Asn541Asn	synonymous_variant	Exon 13 of 17	ENST00000231751.9	NP_002334.2
LTF	NM_001321121.2	c.1617C>T	p.Asn539Asn	synonymous_variant	Exon 13 of 17		NP_001308050.1
LTF	NM_001321122.2	c.1584C>T	p.Asn528Asn	synonymous_variant	Exon 16 of 20		NP_001308051.1
LTF	NM_001199149.2	c.1491C>T	p.Asn497Asn	synonymous_variant	Exon 13 of 17		NP_001186078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTF	ENST00000231751.9	c.1623C>T	p.Asn541Asn	synonymous_variant	Exon 13 of 17	1	NM_002343.6	ENSP00000231751.4

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

GnomAD3 exomes AF: 0.365 AC: 91759 AN: 251442 Hom.: 18492 AF XY: 0.371 AC XY: 50451 AN XY: 135890

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 SAS exome AF: 0.521

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

Gnomad4 AFR exome AF: 0.404

Gnomad4 AMR exome AF: 0.258

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.660

Gnomad4 SAS exome AF: 0.520

Gnomad4 FIN exome AF: 0.392

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.355

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

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.345

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.087
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs1042073; hg19: chr3-46484964; COSMIC: COSV51608438; COSMIC: COSV51608438;