rs406271

chr3-196050105-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001128148.3(TFRC):c.*1837A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 230,654 control chromosomes in the GnomAD database, including 11,404 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 0.32 (7737 hom., cov: 32)
  • Exomes 𝑓: 0.30 (3667 hom.)
• Consequence: TFRC NM_001128148.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

Genes affected

TFRC (HGNC:11763): (transferrin receptor) This gene encodes a cell surface receptor necessary for cellular iron uptake by the process of receptor-mediated endocytosis. This receptor is required for erythropoiesis and neurologic development. Multiple alternatively spliced variants have been identified. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFRC	NM_001128148.3	c.*1837A>G		3_prime_UTR_variant	19/19	ENST00000360110.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFRC	ENST00000360110.9	c.*1837A>G		3_prime_UTR_variant	19/19	1	NM_001128148.3	P2

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48101 AN: 151858 Hom.: 7722 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.293

GnomAD4 exome AF: 0.302 AC: 23751 AN: 78678 Hom.: 3667 Cov.: 0 AF XY: 0.306 AC XY: 11091 AN XY: 36200

Gnomad4 AFR exome AF: 0.311

Gnomad4 AMR exome AF: 0.270

Gnomad4 ASJ exome AF: 0.383

Gnomad4 EAS exome AF: 0.216

Gnomad4 SAS exome AF: 0.351

Gnomad4 FIN exome AF: 0.327

Gnomad4 NFE exome AF: 0.314

Gnomad4 OTH exome AF: 0.303

GnomAD4 genome AF: 0.317 AC: 48159 AN: 151976 Hom.: 7737 Cov.: 32 AF XY: 0.319 AC XY: 23677 AN XY: 74276

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.291

Alfa AF: 0.322 Hom.: 15451

Bravo AF: 0.307

Asia WGS AF: 0.251 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	7.8
Dann	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs406271; hg19: chr3-195776976;