3-196050105-T-C

Variant names:

• chr3-196050105-T-C
• rs406271
• NM_001128148.3:c.*1837A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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]

TFRC Gene-Disease associations (from GenCC):

• TFRC-related combined immunodeficiency

  Inheritance: AR, Unknown Classification: DEFINITIVE, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, PanelApp Australia, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ENSG00000286168 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128148.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFRC	NM_001128148.3	MANE Select	c.*1837A>G		3_prime_UTR	Exon 19 of 19	NP_001121620.1	P02786
	TFRC	NM_003234.4		c.*1837A>G		3_prime_UTR	Exon 19 of 19	NP_003225.2	P02786
	TFRC	NM_001313965.2		c.*1837A>G		3_prime_UTR	Exon 18 of 18	NP_001300894.1	G3V0E5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFRC	ENST00000360110.9	TSL:1 MANE Select	c.*1837A>G		3_prime_UTR	Exon 19 of 19	ENSP00000353224.4	P02786
	TFRC	ENST00000392396.7	TSL:1	c.*1837A>G		3_prime_UTR	Exon 19 of 19	ENSP00000376197.3	P02786
	TFRC	ENST00000420415.5	TSL:1	c.*1837A>G		3_prime_UTR	Exon 18 of 18	ENSP00000390133.1	G3V0E5

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

African (AFR) AF: 0.311 AC: 1175 AN: 3778

American (AMR) AF: 0.270 AC: 652 AN: 2418

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1906 AN: 4982

East Asian (EAS) AF: 0.216 AC: 2399 AN: 11106

South Asian (SAS) AF: 0.351 AC: 240 AN: 684

European-Finnish (FIN) AF: 0.327 AC: 17 AN: 52

Middle Eastern (MID) AF: 0.272 AC: 129 AN: 474

European-Non Finnish (NFE) AF: 0.314 AC: 15241 AN: 48606

Other (OTH) AF: 0.303 AC: 1992 AN: 6578

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

African (AFR) AF: 0.315 AC: 13046 AN: 41442

American (AMR) AF: 0.283 AC: 4320 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1322 AN: 3468

East Asian (EAS) AF: 0.173 AC: 895 AN: 5174

South Asian (SAS) AF: 0.348 AC: 1678 AN: 4822

European-Finnish (FIN) AF: 0.369 AC: 3887 AN: 10544

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21893 AN: 67946

Other (OTH) AF: 0.291 AC: 616 AN: 2114

Alfa AF: 0.319 Hom.: 24647

Bravo AF: 0.307

Asia WGS AF: 0.251 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.8
DANN	Benign	0.70
PhyloP100		-0.027
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs406271;

hg19: chr3-195776976;