rs12330245

Variant names:

• chr3-196063986-G-A
• rs12330245
• NM_001128148.3:c.1318+323C>T

Variant summary

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

The NM_001128148.3(TFRC):​c.1318+323C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,192 control chromosomes in the GnomAD database, including 1,383 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 0.12 (1383 hom., cov: 32)
• Consequence: TFRC NM_001128148.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 4 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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFRC	NM_001128148.3	c.1318+323C>T		intron_variant	Intron 11 of 18	ENST00000360110.9	NP_001121620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFRC	ENST00000360110.9	c.1318+323C>T		intron_variant	Intron 11 of 18	1	NM_001128148.3	ENSP00000353224.4

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17682 AN: 152074 Hom.: 1384 Cov.: 32

Gnomad AFR AF: 0.0308

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0967

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.116 AC: 17676 AN: 152192 Hom.: 1383 Cov.: 32 AF XY: 0.114 AC XY: 8457 AN XY: 74428

African (AFR) AF: 0.0307 AC: 1274 AN: 41540

American (AMR) AF: 0.0966 AC: 1476 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3468

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.116 AC: 561 AN: 4830

European-Finnish (FIN) AF: 0.141 AC: 1497 AN: 10594

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11937 AN: 67974

Other (OTH) AF: 0.129 AC: 273 AN: 2110

Alfa AF: 0.144 Hom.: 703

Bravo AF: 0.109

Asia WGS AF: 0.0630 AC: 217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.1
DANN	Benign	0.73
PhyloP100		0.094
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: rs12330245; hg19: chr3-195790857;