rs12595

Variant names:

• chr3-133777709-T-C
• rs12595
• ENST00000467842.1:n.3527T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-133777709-T-C
• chr3-133777709-T-G

Variant summary

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

The ENST00000467842.1(TF):​n.3527T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 173,654 control chromosomes in the GnomAD database, including 8,700 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 0.30 (7410 hom., cov: 33)
  • Exomes 𝑓: 0.32 (1290 hom.)
• Consequence: TF ENST00000467842.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549
• 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]

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4	c.2062+471T>C		intron_variant	Intron 16 of 16	ENST00000402696.9	NP_001054.2
TF	NM_001354703.2	c.1930+471T>C		intron_variant	Intron 22 of 22		NP_001341632.2
TF	NM_001354704.2	c.1681+471T>C		intron_variant	Intron 15 of 15		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000467842.1	n.3527T>C		non_coding_transcript_exon_variant	Exon 2 of 2	1
TF	ENST00000402696.9	c.2062+471T>C		intron_variant	Intron 16 of 16	1	NM_001063.4	ENSP00000385834.3
TF	ENST00000461695.1	n.*362+471T>C		intron_variant	Intron 6 of 6	3		ENSP00000419714.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45446 AN: 152024 Hom.: 7405 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.321 AC: 6904 AN: 21512 Hom.: 1290 Cov.: 0 AF XY: 0.327 AC XY: 3586 AN XY: 10964

African (AFR) AF: 0.138 AC: 54 AN: 390

American (AMR) AF: 0.413 AC: 1207 AN: 2922

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 73 AN: 352

East Asian (EAS) AF: 0.354 AC: 511 AN: 1442

South Asian (SAS) AF: 0.390 AC: 883 AN: 2266

European-Finnish (FIN) AF: 0.277 AC: 161 AN: 582

Middle Eastern (MID) AF: 0.297 AC: 22 AN: 74

European-Non Finnish (NFE) AF: 0.295 AC: 3662 AN: 12402

Other (OTH) AF: 0.306 AC: 331 AN: 1082

GnomAD4 genome AF: 0.299 AC: 45476 AN: 152142 Hom.: 7410 Cov.: 33 AF XY: 0.300 AC XY: 22348 AN XY: 74374

African (AFR) AF: 0.185 AC: 7671 AN: 41524

American (AMR) AF: 0.381 AC: 5818 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 941 AN: 3468

East Asian (EAS) AF: 0.418 AC: 2164 AN: 5180

South Asian (SAS) AF: 0.421 AC: 2026 AN: 4814

European-Finnish (FIN) AF: 0.286 AC: 3027 AN: 10574

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

European-Non Finnish (NFE) AF: 0.336 AC: 22821 AN: 67978

Other (OTH) AF: 0.308 AC: 651 AN: 2116

Alfa AF: 0.201 Hom.: 529

Bravo AF: 0.300

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.3
DANN	Benign	0.85
PhyloP100		-0.55
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: rs12595; hg19: chr3-133496553; COSMIC: COSV53919024;