rs8177215

Variant names:

• chr3-133754114-G-A
• rs8177215
• NM_001063.4:c.326-381G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-133754114-G-A
• chr3-133754114-G-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.326-381G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0654 in 414,672 control chromosomes in the GnomAD database, including 1,444 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 0.059 (404 hom., cov: 32)
  • Exomes 𝑓: 0.069 (1040 hom.)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443
• Publications: 4 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]

TF Gene-Disease associations (from GenCC):

• atransferrinemia

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Genomics England PanelApp

ENSG00000291042 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4	c.326-381G>A		intron_variant	Intron 3 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.194-381G>A		intron_variant	Intron 9 of 22		NP_001341632.2
TF	NM_001354704.2	c.-56-381G>A		intron_variant	Intron 2 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9	c.326-381G>A		intron_variant	Intron 3 of 16	1	NM_001063.4	ENSP00000385834.3

Frequencies

GnomAD3 genomes AF: 0.0589 AC: 8963 AN: 152098 Hom.: 402 Cov.: 32

Gnomad AFR AF: 0.0386

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0996

Gnomad ASJ AF: 0.0570

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0210

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0495

Gnomad OTH AF: 0.0670

GnomAD4 exome AF: 0.0693 AC: 18175 AN: 262452 Hom.: 1040 Cov.: 0 AF XY: 0.0728 AC XY: 10228 AN XY: 140554

African (AFR) AF: 0.0376 AC: 298 AN: 7916

American (AMR) AF: 0.100 AC: 1219 AN: 12192

Ashkenazi Jewish (ASJ) AF: 0.0626 AC: 460 AN: 7348

East Asian (EAS) AF: 0.236 AC: 3109 AN: 13172

South Asian (SAS) AF: 0.104 AC: 4166 AN: 40172

European-Finnish (FIN) AF: 0.0220 AC: 273 AN: 12430

Middle Eastern (MID) AF: 0.0944 AC: 101 AN: 1070

European-Non Finnish (NFE) AF: 0.0489 AC: 7517 AN: 153744

Other (OTH) AF: 0.0716 AC: 1032 AN: 14408

GnomAD4 genome AF: 0.0589 AC: 8964 AN: 152220 Hom.: 404 Cov.: 32 AF XY: 0.0607 AC XY: 4518 AN XY: 74444

African (AFR) AF: 0.0386 AC: 1603 AN: 41536

American (AMR) AF: 0.0994 AC: 1520 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0570 AC: 198 AN: 3472

East Asian (EAS) AF: 0.241 AC: 1242 AN: 5158

South Asian (SAS) AF: 0.116 AC: 561 AN: 4816

European-Finnish (FIN) AF: 0.0210 AC: 223 AN: 10622

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0496 AC: 3370 AN: 68002

Other (OTH) AF: 0.0691 AC: 146 AN: 2112

Alfa AF: 0.0558 Hom.: 74

Bravo AF: 0.0656

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.0
DANN	Benign	0.73
PhyloP100		-0.44
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: rs8177215; hg19: chr3-133472958;