rs9859260

Variant names:

• chr3-196073676-C-A
• rs9859260
• NM_001128148.3:c.434+254G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-196073676-C-A
• chr3-196073676-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001128148.3(TFRC):​c.434+254G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: TFRC NM_001128148.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158
• Publications: 37 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: G2P, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

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.434+254G>T		intron	N/A	NP_001121620.1	P02786
	TFRC	NM_003234.4		c.434+254G>T		intron	N/A	NP_003225.2	P02786
	TFRC	NM_001313965.2		c.191+254G>T		intron	N/A	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.434+254G>T		intron	N/A	ENSP00000353224.4	P02786
	TFRC	ENST00000392396.7	TSL:1	c.434+254G>T		intron	N/A	ENSP00000376197.3	P02786
	TFRC	ENST00000420415.5	TSL:1	c.191+254G>T		intron	N/A	ENSP00000390133.1	G3V0E5

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 73756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.9
DANN	Benign	0.42
PhyloP100		0.16

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

Other links and lift over

dbSNP: rs9859260; hg19: chr3-195800547;