rs4683235

Variant names:

• chr3-46460441-C-T
• rs4683235
• NM_002343.6:c.44-622G>A

Variant summary

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

The NM_002343.6(LTF):​c.44-622G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 403,422 control chromosomes in the GnomAD database, including 3,053 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 0.12 (1295 hom., cov: 33)
  • Exomes 𝑓: 0.11 (1758 hom.)
• Consequence: LTF NM_002343.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTF	NM_002343.6	c.44-622G>A		intron_variant	Intron 1 of 16	ENST00000231751.9	NP_002334.2
LTF	NM_001321121.2	c.44-622G>A		intron_variant	Intron 1 of 16		NP_001308050.1
LTF	NM_001321122.2	c.5-622G>A		intron_variant	Intron 4 of 19		NP_001308051.1
LTF	NM_001199149.2	c.-89-622G>A		intron_variant	Intron 1 of 16		NP_001186078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTF	ENST00000231751.9	c.44-622G>A		intron_variant	Intron 1 of 16	1	NM_002343.6	ENSP00000231751.4

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18101 AN: 152122 Hom.: 1285 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0803

Gnomad OTH AF: 0.108

GnomAD4 exome AF: 0.106 AC: 26613 AN: 251182 Hom.: 1758 AF XY: 0.103 AC XY: 14494 AN XY: 140954

African (AFR) AF: 0.162 AC: 1193 AN: 7360

American (AMR) AF: 0.223 AC: 4959 AN: 22232

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 1213 AN: 7842

East Asian (EAS) AF: 0.139 AC: 1176 AN: 8434

South Asian (SAS) AF: 0.106 AC: 5187 AN: 48802

European-Finnish (FIN) AF: 0.0691 AC: 758 AN: 10972

Middle Eastern (MID) AF: 0.0845 AC: 143 AN: 1692

European-Non Finnish (NFE) AF: 0.0810 AC: 10671 AN: 131704

Other (OTH) AF: 0.108 AC: 1313 AN: 12144

GnomAD4 genome AF: 0.119 AC: 18148 AN: 152240 Hom.: 1295 Cov.: 33 AF XY: 0.120 AC XY: 8961 AN XY: 74434

African (AFR) AF: 0.159 AC: 6589 AN: 41524

American (AMR) AF: 0.208 AC: 3181 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 543 AN: 3468

East Asian (EAS) AF: 0.151 AC: 783 AN: 5180

South Asian (SAS) AF: 0.106 AC: 514 AN: 4830

European-Finnish (FIN) AF: 0.0649 AC: 688 AN: 10608

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0803 AC: 5465 AN: 68022

Other (OTH) AF: 0.118 AC: 249 AN: 2114

Alfa AF: 0.0954 Hom.: 2505

Bravo AF: 0.127

Asia WGS AF: 0.166 AC: 577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.057
DANN	Benign	0.41
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4683235; hg19: chr3-46501931; COSMIC: COSV51606616; COSMIC: COSV51606616;