rs3804141

Variant names:

• chr3-196070037-C-T
• rs3804141
• NM_001128148.3:c.688-469G>A

Variant summary

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

The NM_001128148.3(TFRC):​c.688-469G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0766 in 152,166 control chromosomes in the GnomAD database, including 566 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 0.077 (566 hom., cov: 32)
• Consequence: TFRC NM_001128148.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFRC	NM_001128148.3	c.688-469G>A		intron_variant	Intron 6 of 18	ENST00000360110.9	NP_001121620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFRC	ENST00000360110.9	c.688-469G>A		intron_variant	Intron 6 of 18	1	NM_001128148.3	ENSP00000353224.4

Frequencies

GnomAD3 genomes AF: 0.0766 AC: 11646 AN: 152048 Hom.: 563 Cov.: 32

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0886

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0745

Gnomad OTH AF: 0.0579

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

GnomAD4 genome AF: 0.0766 AC: 11656 AN: 152166 Hom.: 566 Cov.: 32 AF XY: 0.0825 AC XY: 6137 AN XY: 74388

African (AFR) AF: 0.0363 AC: 1505 AN: 41508

American (AMR) AF: 0.0891 AC: 1362 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 305 AN: 3470

East Asian (EAS) AF: 0.169 AC: 874 AN: 5176

South Asian (SAS) AF: 0.150 AC: 722 AN: 4826

European-Finnish (FIN) AF: 0.157 AC: 1658 AN: 10576

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0745 AC: 5070 AN: 68014

Other (OTH) AF: 0.0597 AC: 126 AN: 2112

Alfa AF: 0.0735 Hom.: 573

Bravo AF: 0.0684

Asia WGS AF: 0.145 AC: 504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.66
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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: rs3804141; hg19: chr3-195796908;