6-133893615-A-T

Position:

• chr6-133893615-A-T

Variant summary

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

The ENST00000237316.3(TCF21):​c.*469A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.939 in 152,254 control chromosomes in the GnomAD database, including 67,182 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 0.94 (67175 hom., cov: 32)
  • Exomes 𝑓: 0.94 (7 hom.)
• Consequence: TCF21 ENST00000237316.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF21	NM_198392.3	c.*469A>T		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF21	ENST00000237316.3	c.*469A>T		3_prime_UTR_variant	3/3	1		P1

Frequencies

GnomAD3 genomes AF: 0.939 AC: 142813 AN: 152120 Hom.: 67114 Cov.: 32

Gnomad AFR AF: 0.983

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.960

Gnomad ASJ AF: 0.896

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.929

Gnomad FIN AF: 0.902

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.920

Gnomad OTH AF: 0.940

GnomAD4 exome AF: 0.938 AC: 15 AN: 16 Hom.: 7 Cov.: 0 AF XY: 1.00 AC XY: 10 AN XY: 10

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.875

GnomAD4 genome AF: 0.939 AC: 142933 AN: 152238 Hom.: 67175 Cov.: 32 AF XY: 0.938 AC XY: 69806 AN XY: 74420

Gnomad4 AFR AF: 0.983

Gnomad4 AMR AF: 0.960

Gnomad4 ASJ AF: 0.896

Gnomad4 EAS AF: 0.886

Gnomad4 SAS AF: 0.930

Gnomad4 FIN AF: 0.902

Gnomad4 NFE AF: 0.920

Gnomad4 OTH AF: 0.940

Alfa AF: 0.926 Hom.: 8117

Bravo AF: 0.947

Asia WGS AF: 0.934 AC: 3248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.47

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: rs4896011; hg19: chr6-134214753;