12-51139075-A-G

Position:

• chr12-51139075-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005653.5(TFCP2):​c.123-20303T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 152,244 control chromosomes in the GnomAD database, including 108 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 0.013 (108 hom., cov: 32)
• Consequence: TFCP2 NM_005653.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

Genes affected

TFCP2 (HGNC:11748): (transcription factor CP2) This gene encodes a transcription factor that binds the alpha-globin promoter and activates transcription of the alpha-globin gene. The encoded protein regulates erythroid gene expression, plays a role in the transcriptional switch of globin gene promoters, and it activates many other cellular and viral gene promoters. The gene product interacts with certain inflammatory response factors, and polymorphisms of this gene may be involved in the pathogenesis of Alzheimer's disease. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFCP2	NM_005653.5	c.123-20303T>C		intron_variant		ENST00000257915.10	NP_005644.2
TFCP2	NM_001173452.2	c.123-20303T>C		intron_variant			NP_001166923.1
TFCP2	NM_001173453.2	c.123-20303T>C		intron_variant			NP_001166924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFCP2	ENST00000257915.10	c.123-20303T>C		intron_variant		1	NM_005653.5	ENSP00000257915.5

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1916 AN: 152126 Hom.: 107 Cov.: 32

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0999

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0175

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00288

Gnomad OTH AF: 0.00909

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

GnomAD4 genome AF: 0.0126 AC: 1925 AN: 152244 Hom.: 108 Cov.: 32 AF XY: 0.0153 AC XY: 1137 AN XY: 74442

Gnomad4 AFR AF: 0.00116

Gnomad4 AMR AF: 0.100

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.0174

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.000847

Gnomad4 NFE AF: 0.00288

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.00724 Hom.: 7

Bravo AF: 0.0191

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.2
DANN	Benign	0.83

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: rs10506300; hg19: chr12-51532858;