3-196073676-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001128148.3(TFRC):​c.434+254G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 151,918 control chromosomes in the GnomAD database, including 19,356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.48 (19356 hom., cov: 31)
• Consequence: TFRC NM_001128148.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-196073676-C-T is Benign according to our data. Variant chr3-196073676-C-T is described in ClinVar as Benign. ClinVar VariationId is 1178062.Status of the report is criteria_provided_single_submitter, 1 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 rank	MANE	Protein	UniProt
TFRC	NM_001128148.3	c.434+254G>A		intron_variant	Intron 4 of 18	ENST00000360110.9	NP_001121620.1
TFRC	NM_003234.4	c.434+254G>A		intron_variant	Intron 4 of 18		NP_003225.2
TFRC	NM_001313965.2	c.191+254G>A		intron_variant	Intron 3 of 17		NP_001300894.1
TFRC	NM_001313966.2	c.-412-1524G>A		intron_variant	Intron 2 of 16		NP_001300895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFRC	ENST00000360110.9	c.434+254G>A		intron_variant	Intron 4 of 18	1	NM_001128148.3	ENSP00000353224.4

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73065 AN: 151800 Hom.: 19359 Cov.: 31

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.481 AC: 73074 AN: 151918 Hom.: 19356 Cov.: 31 AF XY: 0.477 AC XY: 35404 AN XY: 74220

African (AFR) AF: 0.291 AC: 12037 AN: 41422

American (AMR) AF: 0.449 AC: 6852 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1932 AN: 3470

East Asian (EAS) AF: 0.166 AC: 861 AN: 5172

South Asian (SAS) AF: 0.512 AC: 2469 AN: 4818

European-Finnish (FIN) AF: 0.569 AC: 5996 AN: 10532

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41312 AN: 67928

Other (OTH) AF: 0.515 AC: 1086 AN: 2108

Alfa AF: 0.560 Hom.: 73756

Bravo AF: 0.459

Asia WGS AF: 0.365 AC: 1270 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.38
PhyloP100		0.16
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: rs9859260; hg19: chr3-195800547;