NM_001063.4:c.1203+1027G>C

Variant names:

• chr3-133760356-G-C
• rs2718796
• NM_001063.4:c.1203+1027G>C

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+1027G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.964 in 152,458 control chromosomes in the GnomAD database, including 71,027 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 0.96 (70947 hom., cov: 33)
  • Exomes 𝑓: 0.99 (80 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.974 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+1027G>C		intron	N/A	NP_001054.2
	TF	NM_001354703.2		c.1071+1027G>C		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.822+1027G>C		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+1027G>C		intron	N/A	ENSP00000385834.3
	ACSL3P1	ENST00000474389.1	TSL:6	n.57G>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.964 AC: 146743 AN: 152178 Hom.: 70882 Cov.: 33

Gnomad AFR AF: 0.982

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.927

Gnomad ASJ AF: 0.972

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.928

Gnomad FIN AF: 0.990

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.974

Gnomad OTH AF: 0.957

GnomAD4 exome AF: 0.994 AC: 161 AN: 162 Hom.: 80 Cov.: 0 AF XY: 1.00 AC XY: 78 AN XY: 78

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 146 AN: 146

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 14 AN: 14

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.964 AC: 146866 AN: 152296 Hom.: 70947 Cov.: 33 AF XY: 0.962 AC XY: 71649 AN XY: 74456

African (AFR) AF: 0.982 AC: 40796 AN: 41550

American (AMR) AF: 0.927 AC: 14188 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.972 AC: 3376 AN: 3472

East Asian (EAS) AF: 0.777 AC: 4024 AN: 5176

South Asian (SAS) AF: 0.929 AC: 4480 AN: 4824

European-Finnish (FIN) AF: 0.990 AC: 10509 AN: 10620

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.974 AC: 66282 AN: 68038

Other (OTH) AF: 0.955 AC: 2018 AN: 2112

Alfa AF: 0.970 Hom.: 8904

Bravo AF: 0.959

Asia WGS AF: 0.849 AC: 2952 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.27
DANN	Benign	0.39
PhyloP100		-1.4
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: rs2718796; hg19: chr3-133479200; COSMIC: COSV53918843; COSMIC: COSV53918843;