6-133893387-C-G

Variant names:

• chr6-133893387-C-G
• rs12190287
• ENST00000237316.3:c.*241C>G

Variant summary

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

The NM_198392.3(TCF21):​c.*241C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,186 control chromosomes in the GnomAD database, including 8,820 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 0.31 (8812 hom., cov: 33)
  • Exomes 𝑓: 0.38 (8 hom.)
• Consequence: TCF21 NM_198392.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.704
• Publications: 168 publications found

Genes affected

TCF21 (HGNC:11632): (transcription factor 21) TCF21 encodes a transcription factor of the basic helix-loop-helix family. The TCF21 product is mesoderm specific, and expressed in embryonic epicardium, mesenchyme-derived tissues of lung, gut, gonad, and both mesenchymal and glomerular epithelial cells in the kidney. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

TARID (HGNC:50506): (TCF21 antisense RNA inducing promoter demethylation)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198392.3. 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
	TCF21	NM_198392.3		c.*241C>G		3_prime_UTR	Exon 3 of 3	NP_938206.1	O43680

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF21	ENST00000237316.3	TSL:1	c.*241C>G		3_prime_UTR	Exon 3 of 3	ENSP00000237316.3	O43680
	TCF21	ENST00000903811.1		c.*193C>G		3_prime_UTR	Exon 3 of 3	ENSP00000573870.1
	TARID	ENST00000795402.1		n.151+23675G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47160 AN: 151982 Hom.: 8802 Cov.: 33

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.331

GnomAD4 exome AF: 0.375 AC: 33 AN: 88 Hom.: 8 Cov.: 0 AF XY: 0.381 AC XY: 16 AN XY: 42

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.417 AC: 25 AN: 60

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.292 AC: 7 AN: 24

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.310 AC: 47172 AN: 152098 Hom.: 8812 Cov.: 33 AF XY: 0.321 AC XY: 23836 AN XY: 74346

African (AFR) AF: 0.0890 AC: 3697 AN: 41526

American (AMR) AF: 0.411 AC: 6277 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1409 AN: 3472

East Asian (EAS) AF: 0.421 AC: 2169 AN: 5150

South Asian (SAS) AF: 0.503 AC: 2426 AN: 4822

European-Finnish (FIN) AF: 0.462 AC: 4876 AN: 10558

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25154 AN: 67966

Other (OTH) AF: 0.335 AC: 706 AN: 2110

Alfa AF: 0.229 Hom.: 621

Bravo AF: 0.296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.7
DANN	Benign	0.67
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12190287; hg19: chr6-134214525;