3-196027293-A-G

Variant names:

• chr3-196027293-A-G
• rs6782834
• ENST00000650701.3:n.394A>G

Variant summary

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

The ENST00000650701.3(ENSG00000286168):​n.394A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 456,016 control chromosomes in the GnomAD database, including 36,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (14227 hom., cov: 30)
  • Exomes 𝑓: 0.37 (21939 hom.)
• Consequence: ENSG00000286168 ENST00000650701.3 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.66
• Publications: 5 publications found

Genes affected

ENSG00000286168 (HGNC:):

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: DEFINITIVE, MODERATE, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BP6: Variant 3-196027293-A-G is Benign according to our data. Variant chr3-196027293-A-G is described in ClinVar as Benign. ClinVar VariationId is 2637875.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000650701.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000286168	ENST00000650701.3		n.394A>G		non_coding_transcript_exon	Exon 3 of 3
	ENSG00000286168	ENST00000669433.2		n.490A>G		non_coding_transcript_exon	Exon 3 of 3
	TFRC	ENST00000426789.6	TSL:3	n.2112-33T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62140 AN: 151752 Hom.: 14189 Cov.: 30

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.382

GnomAD2 exomes AF: 0.395 AC: 53083 AN: 134504 AF XY: 0.388

Gnomad AFR exome AF: 0.600

Gnomad AMR exome AF: 0.463

Gnomad ASJ exome AF: 0.244

Gnomad EAS exome AF: 0.690

Gnomad FIN exome AF: 0.246

Gnomad NFE exome AF: 0.319

Gnomad OTH exome AF: 0.356

GnomAD4 exome AF: 0.365 AC: 111022 AN: 304144 Hom.: 21939 Cov.: 0 AF XY: 0.365 AC XY: 63294 AN XY: 173216

African (AFR) AF: 0.589 AC: 5077 AN: 8620

American (AMR) AF: 0.464 AC: 12657 AN: 27282

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 2612 AN: 10790

East Asian (EAS) AF: 0.690 AC: 6353 AN: 9210

South Asian (SAS) AF: 0.398 AC: 23760 AN: 59734

European-Finnish (FIN) AF: 0.246 AC: 3146 AN: 12790

Middle Eastern (MID) AF: 0.346 AC: 891 AN: 2574

European-Non Finnish (NFE) AF: 0.324 AC: 51427 AN: 158930

Other (OTH) AF: 0.359 AC: 5099 AN: 14214

GnomAD4 genome AF: 0.410 AC: 62238 AN: 151872 Hom.: 14227 Cov.: 30 AF XY: 0.409 AC XY: 30334 AN XY: 74238

African (AFR) AF: 0.588 AC: 24306 AN: 41352

American (AMR) AF: 0.419 AC: 6386 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 835 AN: 3468

East Asian (EAS) AF: 0.686 AC: 3538 AN: 5158

South Asian (SAS) AF: 0.411 AC: 1978 AN: 4810

European-Finnish (FIN) AF: 0.239 AC: 2524 AN: 10556

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.317 AC: 21553 AN: 67962

Other (OTH) AF: 0.389 AC: 820 AN: 2108

Alfa AF: 0.355 Hom.: 1873

Bravo AF: 0.434

Asia WGS AF: 0.561 AC: 1951 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.3
DANN	Benign	0.15
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs6782834; hg19: chr3-195754164;