3-196069178-G-T

Variant names:

• chr3-196069178-G-T
• rs4927866
• NM_001128148.3:c.801+277C>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.801+277C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 151,918 control chromosomes in the GnomAD database, including 3,131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3131 hom., cov: 32)
• Consequence: TFRC NM_001128148.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.393
• Publications: 7 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=-0.85).
• BP6: Variant 3-196069178-G-T is Benign according to our data. Variant chr3-196069178-G-T is described in ClinVar as Benign. ClinVar VariationId is 1252312.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

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.801+277C>A		intron	N/A	NP_001121620.1
	TFRC	NM_003234.4		c.801+277C>A		intron	N/A	NP_003225.2
	TFRC	NM_001313965.2		c.558+277C>A		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.801+277C>A		intron	N/A	ENSP00000353224.4
	TFRC	ENST00000392396.7	TSL:1	c.801+277C>A		intron	N/A	ENSP00000376197.3
	TFRC	ENST00000420415.5	TSL:1	c.558+277C>A		intron	N/A	ENSP00000390133.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28447 AN: 151800 Hom.: 3132 Cov.: 32

Gnomad AFR AF: 0.0943

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.187 AC: 28450 AN: 151918 Hom.: 3131 Cov.: 32 AF XY: 0.185 AC XY: 13703 AN XY: 74208

African (AFR) AF: 0.0942 AC: 3908 AN: 41466

American (AMR) AF: 0.177 AC: 2701 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1013 AN: 3468

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5166

South Asian (SAS) AF: 0.191 AC: 920 AN: 4816

European-Finnish (FIN) AF: 0.213 AC: 2241 AN: 10508

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16778 AN: 67930

Other (OTH) AF: 0.197 AC: 416 AN: 2110

Alfa AF: 0.224 Hom.: 11143

Bravo AF: 0.179

Asia WGS AF: 0.0830 AC: 290 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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.9
DANN	Benign	0.58
PhyloP100		0.39
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: rs4927866; hg19: chr3-195796049;