dbSNP rs11915082: TFRC:c.-249C>T (chr3-196082268-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001128148.3(TFRC):c.-249C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 205,524 control chromosomes in the GnomAD database, including 11,560 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 0.31 ( 8141 hom., cov: 34)

Exomes 𝑓: 0.34 ( 3419 hom. )

Consequence

TFRC
NM_001128148.3 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.993

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
TFRC	NM_001128148.3 link	c.-249C>T	upstream_gene_variant	ENST00000360110.9	NP_001121620.1	P02786Q7Z3E0
TFRC	NM_003234.4 link	c.-461C>T	upstream_gene_variant		NP_003225.2	P02786A8K6Q8Q7Z3E0
TFRC	NM_001313965.2 link	c.-290C>T	upstream_gene_variant		NP_001300894.1	P02786G3V0E5Q7Z3E0
TFRC	NM_001313966.2 link	c.-697C>T	upstream_gene_variant		NP_001300895.1	P02786A0A8V8TM46B7Z2I6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFRC	ENST00000360110.9 link	c.-249C>T		upstream_gene_variant		1	NM_001128148.3	ENSP00000353224.4		P02786

Frequencies

GnomAD3 genomes

AF:

0.311

AC:

47051

AN:

151142

Hom.:

8133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.179

Gnomad AMI

AF:

0.279

Gnomad AMR

AF:

0.315

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.0779

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.341

Gnomad NFE

AF:

0.399

Gnomad OTH

AF:

0.334

GnomAD4 exome

AF:

0.335

AC:

18199

AN:

54264

Hom.:

3419

AF XY:

0.339

AC XY:

9579

AN XY:

28248

show subpopulations

Gnomad4 AFR exome

AF:

0.147

Gnomad4 AMR exome

AF:

0.290

Gnomad4 ASJ exome

AF:

0.316

Gnomad4 EAS exome

AF:

0.0815

Gnomad4 SAS exome

AF:

0.273

Gnomad4 FIN exome

AF:

0.365

Gnomad4 NFE exome

AF:

0.391

Gnomad4 OTH exome

AF:

0.335

GnomAD4 genome

AF:

0.311

AC:

47072

AN:

151260

Hom.:

8141

Cov.:

AF XY:

0.308

AC XY:

22797

AN XY:

74012

show subpopulations

Gnomad4 AFR

AF:

0.179

Gnomad4 AMR

AF:

0.315

Gnomad4 ASJ

AF:

0.323

Gnomad4 EAS

AF:

0.0777

Gnomad4 SAS

AF:

0.258

Gnomad4 FIN

AF:

0.385

Gnomad4 NFE

AF:

0.399

Gnomad4 OTH

AF:

0.331

Alfa

AF:

0.365

Hom.:

7125

Bravo

AF:

0.298

Asia WGS

AF:

0.182

AC:

636

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

9.7

DANN

Benign

0.86

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over