rs2073495

Variant names:

• chr3-46439467-C-A
• rs2073495
• NM_002343.6:c.1737G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-46439467-C-A
• chr3-46439467-C-G
• chr3-46439467-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002343.6(LTF):​c.1737G>T​(p.Glu579Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000267 in 1,609,048 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00027 (5 hom.)
• Consequence: LTF NM_002343.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.03
• Publications: 45 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0049169958).
• BS2: High Homozygotes in GnomAdExome4 at 5 gene

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.1737G>T	p.Glu579Asp	missense	Exon 15 of 17	NP_002334.2	P02788-1
	LTF	NM_001321121.2		c.1731G>T	p.Glu577Asp	missense	Exon 15 of 17	NP_001308050.1	E7ER44
	LTF	NM_001321122.2		c.1698G>T	p.Glu566Asp	missense	Exon 18 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.1737G>T	p.Glu579Asp	missense	Exon 15 of 17	ENSP00000231751.4	P02788-1
	LTF	ENST00000417439.5	TSL:1	c.1731G>T	p.Glu577Asp	missense	Exon 15 of 17	ENSP00000405546.1	E7ER44
	LTF	ENST00000947212.1		c.1770G>T	p.Glu590Asp	missense	Exon 16 of 18	ENSP00000617271.1

Frequencies

GnomAD3 genomes AF: 0.000270 AC: 41 AN: 152102 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000492 AC: 121 AN: 245726 AF XY: 0.000692

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000120

Gnomad ASJ exome AF: 0.00240

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000261

Gnomad OTH exome AF: 0.000335

GnomAD4 exome AF: 0.000266 AC: 388 AN: 1456828 Hom.: 5 Cov.: 38 AF XY: 0.000364 AC XY: 264 AN XY: 724480

African (AFR) AF: 0.00 AC: 0 AN: 33168

American (AMR) AF: 0.000183 AC: 8 AN: 43792

Ashkenazi Jewish (ASJ) AF: 0.00194 AC: 50 AN: 25818

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00210 AC: 180 AN: 85750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53320

Middle Eastern (MID) AF: 0.00331 AC: 19 AN: 5734

European-Non Finnish (NFE) AF: 0.0000973 AC: 108 AN: 1109478

Other (OTH) AF: 0.000383 AC: 23 AN: 60124

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152220 Hom.: 0 Cov.: 33 AF XY: 0.000390 AC XY: 29 AN XY: 74410

African (AFR) AF: 0.0000481 AC: 2 AN: 41560

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67996

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.0000342 Hom.: 4411

ExAC AF: 0.000478 AC: 58

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.0030
DANN	Benign	0.42
DEOGEN2	Benign	0.086	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.055	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-5.0
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.015
Sift	Benign	0.48	T
Sift4G	Benign	0.48	T
Polyphen		0.0	B
Vest4		0.029
MVP		0.25
MPC		0.064
ClinPred		0.011	T
GERP RS		-10
Varity_R		0.22
gMVP		0.66
Mutation Taster		=99/1	polymorphism

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: rs2073495; hg19: chr3-46480958; COSMIC: COSV51608645;