rs557527

Positions:

• chr3-196053838-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001128148.3(TFRC):​c.1900-280C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,034 control chromosomes in the GnomAD database, including 7,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (7667 hom., cov: 32)
• Consequence: TFRC NM_001128148.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.218

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-196053838-G-A is Benign according to our data. Variant chr3-196053838-G-A is described in ClinVar as [Benign]. Clinvar id is 1280483.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFRC	NM_001128148.3	c.1900-280C>T		intron_variant		ENST00000360110.9	NP_001121620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFRC	ENST00000360110.9	c.1900-280C>T		intron_variant		1	NM_001128148.3	ENSP00000353224	P2

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47858 AN: 151916 Hom.: 7656 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.315 AC: 47905 AN: 152034 Hom.: 7667 Cov.: 32 AF XY: 0.317 AC XY: 23562 AN XY: 74306

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.290

Alfa AF: 0.326 Hom.: 1052

Bravo AF: 0.305

Asia WGS AF: 0.241 AC: 840 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.81
CADD	Benign	1.9
DANN	Benign	0.31

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: rs557527; hg19: chr3-195780709;