NM_005653.5:c.*788T>C

Variant names:

• chr12-51094453-A-G
• rs10876135
• NM_005653.5:c.*788T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005653.5. 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
	TFCP2	NM_005653.5	MANE Select	c.*788T>C		3_prime_UTR	Exon 15 of 15	NP_005644.2
	TFCP2	NM_001173452.2		c.*788T>C		3_prime_UTR	Exon 15 of 15	NP_001166923.1	Q12800-4
	TFCP2	NM_001173453.2		c.*788T>C		3_prime_UTR	Exon 14 of 14	NP_001166924.1	Q12800-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFCP2	ENST00000257915.10	TSL:1 MANE Select	c.*788T>C		3_prime_UTR	Exon 15 of 15	ENSP00000257915.5	Q12800-1
	TFCP2	ENST00000930488.1		c.*788T>C		3_prime_UTR	Exon 16 of 16	ENSP00000600547.1
	TFCP2	ENST00000930487.1		c.*788T>C		3_prime_UTR	Exon 16 of 16	ENSP00000600546.1

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 4 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.875 AC: 7 AN: 8

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.735 AC: 30488 AN: 41474

American (AMR) AF: 0.806 AC: 12306 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.921 AC: 3199 AN: 3472

East Asian (EAS) AF: 0.837 AC: 4333 AN: 5176

South Asian (SAS) AF: 0.930 AC: 4475 AN: 4814

European-Finnish (FIN) AF: 0.954 AC: 10123 AN: 10606

Middle Eastern (MID) AF: 0.928 AC: 271 AN: 292

European-Non Finnish (NFE) AF: 0.958 AC: 65177 AN: 68028

Other (OTH) AF: 0.895 AC: 1893 AN: 2114

Alfa AF: 0.929 Hom.: 108099

Bravo AF: 0.854

Asia WGS AF: 0.871 AC: 3031 AN: 3478

ClinVar

ClinVar submissions

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	-0.77
CADD	Benign	1.8
DANN	Benign	0.73
PhyloP100		-0.47
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: rs10876135; hg19: chr12-51488236;