NM_002343.6:c.1212+104T>C

Variant names:

• chr3-46448759-A-G
• rs1475967
• NM_002343.6:c.1212+104T>C

Variant summary

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

The NM_002343.6(LTF):​c.1212+104T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 1,383,542 control chromosomes in the GnomAD database, including 108,728 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 0.51 (23728 hom., cov: 33)
  • Exomes 𝑓: 0.35 (85000 hom.)
• Consequence: LTF NM_002343.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.47
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTF	NM_002343.6	MANE Select	c.1212+104T>C		intron	N/A	NP_002334.2
	LTF	NM_001321121.2		c.1206+110T>C		intron	N/A	NP_001308050.1
	LTF	NM_001321122.2		c.1173+104T>C		intron	N/A	NP_001308051.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTF	ENST00000231751.9	TSL:1 MANE Select	c.1212+104T>C		intron	N/A	ENSP00000231751.4
	LTF	ENST00000417439.5	TSL:1	c.1206+110T>C		intron	N/A	ENSP00000405546.1
	LTF	ENST00000443496.5	TSL:2	c.1173+104T>C		intron	N/A	ENSP00000397427.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76925 AN: 152022 Hom.: 23660 Cov.: 33

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.448

GnomAD4 exome AF: 0.354 AC: 436252 AN: 1231402 Hom.: 85000 AF XY: 0.358 AC XY: 219267 AN XY: 611766

African (AFR) AF: 0.893 AC: 23441 AN: 26248

American (AMR) AF: 0.433 AC: 9969 AN: 23010

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 7943 AN: 21526

East Asian (EAS) AF: 0.603 AC: 20485 AN: 33970

South Asian (SAS) AF: 0.524 AC: 36385 AN: 69380

European-Finnish (FIN) AF: 0.401 AC: 18129 AN: 45186

Middle Eastern (MID) AF: 0.459 AC: 2352 AN: 5122

European-Non Finnish (NFE) AF: 0.311 AC: 297179 AN: 955058

Other (OTH) AF: 0.392 AC: 20369 AN: 51902

GnomAD4 genome AF: 0.507 AC: 77060 AN: 152140 Hom.: 23728 Cov.: 33 AF XY: 0.511 AC XY: 38025 AN XY: 74384

African (AFR) AF: 0.866 AC: 35958 AN: 41524

American (AMR) AF: 0.454 AC: 6942 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1283 AN: 3468

East Asian (EAS) AF: 0.592 AC: 3058 AN: 5164

South Asian (SAS) AF: 0.539 AC: 2604 AN: 4828

European-Finnish (FIN) AF: 0.401 AC: 4246 AN: 10588

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.317 AC: 21566 AN: 67968

Other (OTH) AF: 0.454 AC: 959 AN: 2112

Alfa AF: 0.276 Hom.: 754

Bravo AF: 0.522

Asia WGS AF: 0.583 AC: 2023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.34
DANN	Benign	0.33
PhyloP100		-4.5
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: rs1475967; hg19: chr3-46490250;