rs10247962

Variant names:

• chr7-100622306-G-A
• rs10247962
• NM_003227.4:c.2137-1180C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-100622306-G-A
• chr7-100622306-G-C
• chr7-100622306-G-T

Variant summary

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

The NM_003227.4(TFR2):​c.2137-1180C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 152,152 control chromosomes in the GnomAD database, including 58,539 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 0.87 (58539 hom., cov: 32)
• Consequence: TFR2 NM_003227.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109
• Publications: 7 publications found

Genes affected

TFR2 (HGNC:11762): (transferrin receptor 2) This gene encodes a single-pass type II membrane protein, which is a member of the transferrin receptor-like family. This protein mediates cellular uptake of transferrin-bound iron, and may be involved in iron metabolism, hepatocyte function and erythrocyte differentiation. Mutations in this gene have been associated with hereditary hemochromatosis type III. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, May 2011]

TFR2 Gene-Disease associations (from GenCC):

• hemochromatosis type 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, PanelApp Australia

LOC124901709 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003227.4. 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
	TFR2	NM_003227.4	MANE Select	c.2137-1180C>T		intron	N/A	NP_003218.2
	TFR2	NM_001206855.3		c.1624-1180C>T		intron	N/A	NP_001193784.1	Q9UP52-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFR2	ENST00000223051.8	TSL:1 MANE Select	c.2137-1180C>T		intron	N/A	ENSP00000223051.3	Q9UP52-1
	TFR2	ENST00000855275.1		c.2233-1180C>T		intron	N/A	ENSP00000525334.1
	TFR2	ENST00000855257.1		c.2230-1180C>T		intron	N/A	ENSP00000525316.1

Frequencies

GnomAD3 genomes AF: 0.875 AC: 132974 AN: 152034 Hom.: 58487 Cov.: 32

Gnomad AFR AF: 0.965

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.872

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

GnomAD4 genome AF: 0.875 AC: 133085 AN: 152152 Hom.: 58539 Cov.: 32 AF XY: 0.872 AC XY: 64845 AN XY: 74382

African (AFR) AF: 0.965 AC: 40070 AN: 41544

American (AMR) AF: 0.903 AC: 13786 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.883 AC: 3065 AN: 3472

East Asian (EAS) AF: 0.904 AC: 4680 AN: 5176

South Asian (SAS) AF: 0.759 AC: 3661 AN: 4822

European-Finnish (FIN) AF: 0.784 AC: 8307 AN: 10590

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.835 AC: 56727 AN: 67974

Other (OTH) AF: 0.872 AC: 1840 AN: 2110

Alfa AF: 0.855 Hom.: 8133

Bravo AF: 0.890

Asia WGS AF: 0.833 AC: 2898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.6
DANN	Benign	0.40
PhyloP100		0.11
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: rs10247962; hg19: chr7-100219929;