chr3-46447363-T-C

Variant names:

• chr3-46447363-T-C
• rs2239692
• NM_002343.6:c.1248A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_002343.6(LTF):​c.1248A>G​(p.Gly416Gly) 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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 15 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.237 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.1248A>G	p.Gly416Gly	synonymous	Exon 10 of 17	NP_002334.2	P02788-1
	LTF	NM_001321121.2		c.1242A>G	p.Gly414Gly	synonymous	Exon 10 of 17	NP_001308050.1	E7ER44
	LTF	NM_001321122.2		c.1209A>G	p.Gly403Gly	synonymous	Exon 13 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.1248A>G	p.Gly416Gly	synonymous	Exon 10 of 17	ENSP00000231751.4	P02788-1
	LTF	ENST00000417439.5	TSL:1	c.1242A>G	p.Gly414Gly	synonymous	Exon 10 of 17	ENSP00000405546.1	E7ER44
	LTF	ENST00000947212.1		c.1248A>G	p.Gly416Gly	synonymous	Exon 10 of 18	ENSP00000617271.1

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

GnomAD2 exomes AF: 0.145 AC: 36551 AN: 251428 AF XY: 0.150

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 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

African (AFR) AF: 0.189 AC: 6309 AN: 33454

American (AMR) AF: 0.103 AC: 4608 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 3355 AN: 26122

East Asian (EAS) AF: 0.230 AC: 9110 AN: 39686

South Asian (SAS) AF: 0.250 AC: 21587 AN: 86220

European-Finnish (FIN) AF: 0.175 AC: 9352 AN: 53388

Middle Eastern (MID) AF: 0.161 AC: 928 AN: 5768

European-Non Finnish (NFE) AF: 0.111 AC: 123710 AN: 1111262

Other (OTH) AF: 0.139 AC: 8390 AN: 60352

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

African (AFR) AF: 0.179 AC: 7448 AN: 41506

American (AMR) AF: 0.110 AC: 1682 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 467 AN: 3472

East Asian (EAS) AF: 0.221 AC: 1140 AN: 5166

South Asian (SAS) AF: 0.248 AC: 1197 AN: 4822

European-Finnish (FIN) AF: 0.183 AC: 1942 AN: 10588

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7584 AN: 67990

Other (OTH) AF: 0.128 AC: 270 AN: 2104

Alfa AF: 0.121 Hom.: 707

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.6
DANN	Benign	0.87
PhyloP100		-1.0
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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