3-196058126-G-A

Position:

• chr3-196058126-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001128148.3(TFRC):​c.1677+158C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 518,240 control chromosomes in the GnomAD database, including 26,598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (7650 hom., cov: 31)
  • Exomes 𝑓: 0.32 (18948 hom.)
• Consequence: TFRC NM_001128148.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.548

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-196058126-G-A is Benign according to our data. Variant chr3-196058126-G-A is described in ClinVar as [Benign]. Clinvar id is 1236742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFRC	NM_001128148.3	c.1677+158C>T		intron_variant		ENST00000360110.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFRC	ENST00000360110.9	c.1677+158C>T		intron_variant		1	NM_001128148.3	P2

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47804 AN: 151790 Hom.: 7639 Cov.: 31

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.292

GnomAD4 exome AF: 0.315 AC: 115514 AN: 366332 Hom.: 18948 Cov.: 5 AF XY: 0.319 AC XY: 61264 AN XY: 192320

Gnomad4 AFR exome AF: 0.298

Gnomad4 AMR exome AF: 0.267

Gnomad4 ASJ exome AF: 0.382

Gnomad4 EAS exome AF: 0.205

Gnomad4 SAS exome AF: 0.351

Gnomad4 FIN exome AF: 0.380

Gnomad4 NFE exome AF: 0.317

Gnomad4 OTH exome AF: 0.303

GnomAD4 genome AF: 0.315 AC: 47851 AN: 151908 Hom.: 7650 Cov.: 31 AF XY: 0.317 AC XY: 23530 AN XY: 74246

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.290

Alfa AF: 0.318 Hom.: 1348

Bravo AF: 0.305

Asia WGS AF: 0.241 AC: 840 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.77
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs3933; hg19: chr3-195784997; COSMIC: COSV64056390; COSMIC: COSV64056390;