3-196058126-G-C

Variant names:

• chr3-196058126-G-C
• rs3933
• NM_001128148.3:c.1677+158C>G

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.1677+158C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000544 in 367,500 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000054 (0 hom.)
• Consequence: TFRC NM_001128148.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548
• Publications: 0 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: MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

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=-0.92).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFRC	NM_001128148.3	MANE Select	c.1677+158C>G		intron	N/A	NP_001121620.1
	TFRC	NM_003234.4		c.1677+158C>G		intron	N/A	NP_003225.2
	TFRC	NM_001313965.2		c.1434+158C>G		intron	N/A	NP_001300894.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFRC	ENST00000360110.9	TSL:1 MANE Select	c.1677+158C>G		intron	N/A	ENSP00000353224.4
	TFRC	ENST00000392396.7	TSL:1	c.1677+158C>G		intron	N/A	ENSP00000376197.3
	TFRC	ENST00000420415.5	TSL:1	c.1434+158C>G		intron	N/A	ENSP00000390133.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000544 AC: 2 AN: 367500 Hom.: 0 Cov.: 5 AF XY: 0.00000518 AC XY: 1 AN XY: 192924

African (AFR) AF: 0.00 AC: 0 AN: 9820

American (AMR) AF: 0.00 AC: 0 AN: 12692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10712

East Asian (EAS) AF: 0.00 AC: 0 AN: 26358

South Asian (SAS) AF: 0.0000828 AC: 2 AN: 24154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3124

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 221962

Other (OTH) AF: 0.00 AC: 0 AN: 20956

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.28
DANN	Benign	0.42
PhyloP100		-0.55

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: rs3933; hg19: chr3-195784997;