3-46472487-A-G

Variant names:

• chr3-46472487-A-G
• rs7639243
• NM_001321122.2:c.-319-2021T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001321122.2(LTF):​c.-319-2021T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 145,722 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000027 (0 hom., cov: 24)
• Consequence: LTF NM_001321122.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 8 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321122.2. 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_001321122.2		c.-319-2021T>C		intron	N/A	NP_001308051.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTF	ENST00000443496.5	TSL:2	c.-319-2021T>C		intron	N/A	ENSP00000397427.1	E7EQB2
	LTF	ENST00000498301.1	TSL:4	c.-64-4168T>C		intron	N/A	ENSP00000508000.1	A0A804HKN5

Frequencies

GnomAD3 genomes AF: 0.0000274 AC: 4 AN: 145722 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000305

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000274 AC: 4 AN: 145722 Hom.: 0 Cov.: 24 AF XY: 0.0000283 AC XY: 2 AN XY: 70678

African (AFR) AF: 0.0000250 AC: 1 AN: 40014

American (AMR) AF: 0.00 AC: 0 AN: 14902

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3384

East Asian (EAS) AF: 0.000199 AC: 1 AN: 5030

South Asian (SAS) AF: 0.00 AC: 0 AN: 4468

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000305 AC: 2 AN: 65484

Other (OTH) AF: 0.00 AC: 0 AN: 2010

Alfa AF: 0.00 Hom.: 10247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.17
DANN	Benign	0.74
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs7639243; hg19: chr3-46513977;