rs9846149

Positions:

• chr3-196060437-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001128148.3(TFRC):​c.1469-190G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 576,184 control chromosomes in the GnomAD database, including 86,710 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (19348 hom., cov: 31)
  • Exomes 𝑓: 0.55 (67362 hom.)
• Consequence: TFRC NM_001128148.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.412

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-196060437-C-G is Benign according to our data. Variant chr3-196060437-C-G is described in ClinVar as [Benign]. Clinvar id is 1280043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFRC	NM_001128148.3	c.1469-190G>C		intron_variant		ENST00000360110.9	NP_001121620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFRC	ENST00000360110.9	c.1469-190G>C		intron_variant		1	NM_001128148.3	ENSP00000353224.4

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73002 AN: 151836 Hom.: 19351 Cov.: 31

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.520

GnomAD4 exome AF: 0.549 AC: 232833 AN: 424230 Hom.: 67362 Cov.: 4 AF XY: 0.549 AC XY: 123784 AN XY: 225448

Gnomad4 AFR exome AF: 0.290

Gnomad4 AMR exome AF: 0.419

Gnomad4 ASJ exome AF: 0.543

Gnomad4 EAS exome AF: 0.209

Gnomad4 SAS exome AF: 0.525

Gnomad4 FIN exome AF: 0.555

Gnomad4 NFE exome AF: 0.611

Gnomad4 OTH exome AF: 0.545

GnomAD4 genome AF: 0.480 AC: 73011 AN: 151954 Hom.: 19348 Cov.: 31 AF XY: 0.477 AC XY: 35394 AN XY: 74250

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.514

Alfa AF: 0.538 Hom.: 2942

Bravo AF: 0.459

Asia WGS AF: 0.363 AC: 1265 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs9846149; hg19: chr3-195787308; COSMIC: COSV64054869; COSMIC: COSV64054869;