3-196048004-G-GGAAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000698274.1(TFRC):c.2040+5413_2040+5414insTTTTTC variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.25 (3392 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: TFRC ENST00000698274.1 intron, NMD_transcript
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.415

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd at 3398 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFRC	ENST00000698274.1	c.2040+5413_2040+5414insTTTTTC		intron_variant, NMD_transcript_variant
TFRC	ENST00000426789.6	n.2111+5413_2111+5414insTTTTTC		intron_variant, non_coding_transcript_variant		3
TFRC	ENST00000698275.1	n.2216+5413_2216+5414insTTTTTC		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.254 AC: 23981 AN: 94324 Hom.: 3398 Cov.: 0

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.00937

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.252

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.254 AC: 23970 AN: 94296 Hom.: 3392 Cov.: 0 AF XY: 0.253 AC XY: 11107 AN XY: 43888

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.00941

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.252

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

-

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1553789804; hg19: chr3-195774875;