rs3933

Variant names:

• chr3-196058126-G-A
• rs3933
• NM_001128148.3:c.1677+158C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-196058126-G-A
• chr3-196058126-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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 -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 VariationId 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.

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.1677+158C>T		intron	N/A	NP_001121620.1
	TFRC	NM_003234.4		c.1677+158C>T		intron	N/A	NP_003225.2
	TFRC	NM_001313965.2		c.1434+158C>T		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.1677+158C>T		intron	N/A	ENSP00000353224.4
	TFRC	ENST00000392396.7	TSL:1	c.1677+158C>T		intron	N/A	ENSP00000376197.3
	TFRC	ENST00000420415.5	TSL:1	c.1434+158C>T		intron	N/A	ENSP00000390133.1

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

African (AFR) AF: 0.298 AC: 2916 AN: 9788

American (AMR) AF: 0.267 AC: 3377 AN: 12644

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 4076 AN: 10670

East Asian (EAS) AF: 0.205 AC: 5383 AN: 26290

South Asian (SAS) AF: 0.351 AC: 8449 AN: 24080

European-Finnish (FIN) AF: 0.380 AC: 14283 AN: 37626

Middle Eastern (MID) AF: 0.219 AC: 682 AN: 3116

European-Non Finnish (NFE) AF: 0.317 AC: 70019 AN: 221220

Other (OTH) AF: 0.303 AC: 6329 AN: 20898

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

African (AFR) AF: 0.310 AC: 12833 AN: 41440

American (AMR) AF: 0.282 AC: 4307 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3468

East Asian (EAS) AF: 0.171 AC: 883 AN: 5172

South Asian (SAS) AF: 0.341 AC: 1640 AN: 4816

European-Finnish (FIN) AF: 0.370 AC: 3890 AN: 10520

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.322 AC: 21870 AN: 67922

Other (OTH) AF: 0.290 AC: 612 AN: 2110

Alfa AF: 0.318 Hom.: 1390

Bravo AF: 0.305

Asia WGS AF: 0.241 AC: 840 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.77
DANN	Benign	0.38
PhyloP100		-0.55
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: rs3933; hg19: chr3-195784997; COSMIC: COSV64056390; COSMIC: COSV64056390;