12-51094453-A-G

Position:

• chr12-51094453-A-G

Variant summary

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

The NM_005653.5(TFCP2):​c.*788T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 152,174 control chromosomes in the GnomAD database, including 59,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (59070 hom., cov: 31)
  • Exomes 𝑓: 0.88 (6 hom.)
• Consequence: TFCP2 NM_005653.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.474

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 12-51094453-A-G is Benign according to our data. Variant chr12-51094453-A-G is described in ClinVar as [Benign]. Clinvar id is 1257935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFCP2	NM_005653.5	c.*788T>C		3_prime_UTR_variant	15/15	ENST00000257915.10	NP_005644.2
TFCP2	NM_001173452.2	c.*788T>C		3_prime_UTR_variant	15/15		NP_001166923.1
TFCP2	NM_001173453.2	c.*788T>C		3_prime_UTR_variant	14/14		NP_001166924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFCP2	ENST00000257915	c.*788T>C		3_prime_UTR_variant	15/15	1	NM_005653.5	ENSP00000257915.5
TFCP2	ENST00000685804.1	n.*2172T>C		non_coding_transcript_exon_variant	16/16			ENSP00000509750.1
TFCP2	ENST00000685804.1	n.*2172T>C		3_prime_UTR_variant	16/16			ENSP00000509750.1

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133001 AN: 152040 Hom.: 59029 Cov.: 31

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.921

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.930

Gnomad FIN AF: 0.954

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.958

Gnomad OTH AF: 0.894

GnomAD4 exome AF: 0.875 AC: 14 AN: 16 Hom.: 6 Cov.: 0 AF XY: 0.900 AC XY: 9 AN XY: 10

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.875

GnomAD4 genome AF: 0.875 AC: 133094 AN: 152158 Hom.: 59070 Cov.: 31 AF XY: 0.875 AC XY: 65097 AN XY: 74374

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.806

Gnomad4 ASJ AF: 0.921

Gnomad4 EAS AF: 0.837

Gnomad4 SAS AF: 0.930

Gnomad4 FIN AF: 0.954

Gnomad4 NFE AF: 0.958

Gnomad4 OTH AF: 0.895

Alfa AF: 0.937 Hom.: 86673

Bravo AF: 0.854

Asia WGS AF: 0.871 AC: 3031 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	Jan 11, 2019	This variant is associated with the following publications: (PMID: 28286146) -
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	-0.77
CADD	Benign	1.8
DANN	Benign	0.73

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: rs10876135; hg19: chr12-51488236;