rs2239692

Positions:

• chr3-46447363-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002343.6(LTF):​c.1248A>G​(p.Gly416=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,613,116 control chromosomes in the GnomAD database, including 15,268 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 0.14 (1747 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13521 hom.)
• Consequence: LTF NM_002343.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTF	NM_002343.6	c.1248A>G	p.Gly416=	synonymous_variant	10/17	ENST00000231751.9
LTF	NM_001321121.2	c.1242A>G	p.Gly414=	synonymous_variant	10/17
LTF	NM_001321122.2	c.1209A>G	p.Gly403=	synonymous_variant	13/20
LTF	NM_001199149.2	c.1116A>G	p.Gly372=	synonymous_variant	10/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTF	ENST00000231751.9	c.1248A>G	p.Gly416=	synonymous_variant	10/17	1	NM_002343.6	P3

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21904 AN: 152022 Hom.: 1741 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.119

GnomAD3 exomes AF: 0.145 AC: 36551 AN: 251428 Hom.: 3062 AF XY: 0.150 AC XY: 20415 AN XY: 135882

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.0984

Gnomad ASJ exome AF: 0.126

Gnomad EAS exome AF: 0.217

Gnomad SAS exome AF: 0.256

Gnomad FIN exome AF: 0.177

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.127

GnomAD4 exome AF: 0.128 AC: 187349 AN: 1460976 Hom.: 13521 Cov.: 31 AF XY: 0.132 AC XY: 95858 AN XY: 726804

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.144 AC: 21934 AN: 152140 Hom.: 1747 Cov.: 32 AF XY: 0.150 AC XY: 11137 AN XY: 74390

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.128

Alfa AF: 0.122 Hom.: 550

Bravo AF: 0.137

Asia WGS AF: 0.239 AC: 831 AN: 3478

EpiCase AF: 0.112

EpiControl AF: 0.110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.6
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.25		Position offset: 35
DS_DG_spliceai		0.20		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2239692; hg19: chr3-46488854; COSMIC: COSV51606575;