rs7639243

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-46472487-A-C
• chr3-46472487-A-G
• chr3-46472487-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321122.2(LTF):​c.-319-2021T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 145,714 control chromosomes in the GnomAD database, including 42,915 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 0.77 (42915 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

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>G		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>G		intron	N/A	ENSP00000397427.1	E7EQB2
	LTF	ENST00000498301.1	TSL:4	c.-64-4168T>G		intron	N/A	ENSP00000508000.1	A0A804HKN5

Frequencies

GnomAD3 genomes AF: 0.770 AC: 112166 AN: 145594 Hom.: 42852 Cov.: 24

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.921

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.763

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

GnomAD4 genome AF: 0.771 AC: 112290 AN: 145714 Hom.: 42915 Cov.: 24 AF XY: 0.772 AC XY: 54617 AN XY: 70750

African (AFR) AF: 0.878 AC: 35201 AN: 40100

American (AMR) AF: 0.804 AC: 11981 AN: 14908

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2499 AN: 3380

East Asian (EAS) AF: 0.921 AC: 4617 AN: 5014

South Asian (SAS) AF: 0.789 AC: 3517 AN: 4458

European-Finnish (FIN) AF: 0.696 AC: 6454 AN: 9268

Middle Eastern (MID) AF: 0.734 AC: 201 AN: 274

European-Non Finnish (NFE) AF: 0.698 AC: 45649 AN: 65428

Other (OTH) AF: 0.766 AC: 1554 AN: 2028

Alfa AF: 0.684 Hom.: 10247

Bravo AF: 0.770

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.16
DANN	Benign	0.38
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;