rs10247962

chr7-100622306-G-Achr7-100622306-G-Cchr7-100622306-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC124901709 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFR2	NM_003227.4	c.2137-1180C>T		intron_variant		ENST00000223051.8
LOC124901709	XR_007060454.1	n.185G>A		non_coding_transcript_exon_variant	1/3
TFR2	NM_001206855.3	c.1624-1180C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFR2	ENST00000223051.8	c.2137-1180C>T		intron_variant		1	NM_003227.4	P1

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

Gnomad4 AFR AF: 0.965

Gnomad4 AMR AF: 0.903

Gnomad4 ASJ AF: 0.883

Gnomad4 EAS AF: 0.904

Gnomad4 SAS AF: 0.759

Gnomad4 FIN AF: 0.784

Gnomad4 NFE AF: 0.835

Gnomad4 OTH AF: 0.872

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	3.6
Dann	Benign	0.40

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: rs10247962; hg19: chr7-100219929;