NM_001063.4:c.1203+1453C>T

Variant names:

• chr3-133760782-C-T
• rs8177248
• NM_001063.4:c.1203+1453C>T

Variant summary

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

The NM_001063.4(TF):​c.1203+1453C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 162,034 control chromosomes in the GnomAD database, including 7,160 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 0.28 (6994 hom., cov: 33)
  • Exomes 𝑓: 0.17 (166 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 9 publications found

Genes affected

TF (HGNC:11740): (transferrin) This gene encodes a glycoprotein with an approximate molecular weight of 76.5 kDa. It is thought to have been created as a result of an ancient gene duplication event that led to generation of homologous C and N-terminal domains each of which binds one ion of ferric iron. The function of this protein is to transport iron from the intestine, reticuloendothelial system, and liver parenchymal cells to all proliferating cells in the body. This protein may also have a physiologic role as granulocyte/pollen-binding protein (GPBP) involved in the removal of certain organic matter and allergens from serum. [provided by RefSeq, Sep 2009]

ACSL3P1 (HGNC:56529): (ACSL3 pseudogene 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001063.4. 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
	TF	NM_001063.4	MANE Select	c.1203+1453C>T		intron	N/A	NP_001054.2
	TF	NM_001354703.2		c.1071+1453C>T		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.822+1453C>T		intron	N/A	NP_001341633.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	ENST00000402696.9	TSL:1 MANE Select	c.1203+1453C>T		intron	N/A	ENSP00000385834.3
	ACSL3P1	ENST00000474389.1	TSL:6	n.483C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42950 AN: 151990 Hom.: 6988 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.170 AC: 1684 AN: 9926 Hom.: 166 Cov.: 0 AF XY: 0.168 AC XY: 928 AN XY: 5538

African (AFR) AF: 0.0300 AC: 3 AN: 100

American (AMR) AF: 0.193 AC: 90 AN: 466

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 32 AN: 226

East Asian (EAS) AF: 0.204 AC: 44 AN: 216

South Asian (SAS) AF: 0.154 AC: 80 AN: 518

European-Finnish (FIN) AF: 0.200 AC: 851 AN: 4260

Middle Eastern (MID) AF: 0.0515 AC: 14 AN: 272

European-Non Finnish (NFE) AF: 0.145 AC: 507 AN: 3500

Other (OTH) AF: 0.171 AC: 63 AN: 368

GnomAD4 genome AF: 0.283 AC: 42984 AN: 152108 Hom.: 6994 Cov.: 33 AF XY: 0.286 AC XY: 21257 AN XY: 74360

African (AFR) AF: 0.126 AC: 5234 AN: 41510

American (AMR) AF: 0.374 AC: 5720 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 992 AN: 3468

East Asian (EAS) AF: 0.424 AC: 2193 AN: 5168

South Asian (SAS) AF: 0.422 AC: 2037 AN: 4824

European-Finnish (FIN) AF: 0.287 AC: 3030 AN: 10562

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22796 AN: 67976

Other (OTH) AF: 0.298 AC: 629 AN: 2112

Alfa AF: 0.254 Hom.: 1680

Bravo AF: 0.281

Asia WGS AF: 0.393 AC: 1365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.2
DANN	Benign	0.61
PhyloP100		0.029
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs8177248; hg19: chr3-133479626;