3-196024759-T-C

Variant names:

• chr3-196024759-T-C
• rs4927850
• ENST00000650701.3:n.175-1257T>C

Variant summary

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

The ENST00000650701.3(ENSG00000286168):​n.175-1257T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 152,094 control chromosomes in the GnomAD database, including 38,581 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 0.71 (38581 hom., cov: 33)
• Consequence: ENSG00000286168 ENST00000650701.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02
• Publications: 20 publications found

Genes affected

ENSG00000286168 (HGNC:):

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: MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124909478	XR_007096229.1	n.1115-801A>G		intron_variant	Intron 1 of 2
LOC124909478	XR_007096230.1	n.1115-801A>G		intron_variant	Intron 1 of 3
LOC124909478	XR_007096231.1	n.1114+2378A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000286168	ENST00000650701.3	n.175-1257T>C		intron_variant	Intron 1 of 2
ENSG00000286168	ENST00000669433.2	n.179-1257T>C		intron_variant	Intron 1 of 2
TFRC	ENST00000698274.1	n.*37+2378A>G		intron_variant	Intron 19 of 20			ENSP00000513645.1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107812 AN: 151976 Hom.: 38536 Cov.: 33

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.730

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.710 AC: 107916 AN: 152094 Hom.: 38581 Cov.: 33 AF XY: 0.707 AC XY: 52540 AN XY: 74318

African (AFR) AF: 0.784 AC: 32524 AN: 41498

American (AMR) AF: 0.736 AC: 11233 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2194 AN: 3470

East Asian (EAS) AF: 0.759 AC: 3921 AN: 5168

South Asian (SAS) AF: 0.676 AC: 3261 AN: 4824

European-Finnish (FIN) AF: 0.624 AC: 6588 AN: 10552

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45887 AN: 67992

Other (OTH) AF: 0.732 AC: 1548 AN: 2114

Alfa AF: 0.678 Hom.: 47378

Bravo AF: 0.724

Asia WGS AF: 0.741 AC: 2577 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.33
PhyloP100		-3.0

Splicing

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

Other links and lift over

dbSNP: rs4927850; hg19: chr3-195751630;