3-196024759-T-C

Variant names:

• chr3-196024759-T-C
• rs4927850
• ENST00000650701.2:n.150-1257T>C

Variant summary

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

The ENST00000698274.1(TFRC):​n.*37+2378A>G 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: TFRC ENST00000698274.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02

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]

ACMG classification

Verdict is Benign. Variant got -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	ENST00000650701.2	n.150-1257T>C		intron_variant	Intron 1 of 2
ENSG00000286168	ENST00000669433.1	n.155-1257T>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

Gnomad4 AFR AF: 0.784

Gnomad4 AMR AF: 0.736

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.732

Alfa AF: 0.677 Hom.: 32955

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4927850; hg19: chr3-195751630;