6-133893089-G-A

Variant names:

• chr6-133893089-G-A
• rs2327433
• ENST00000237316.3:c.*9-66G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000237316.3(TCF21):​c.*9-66G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 152,332 control chromosomes in the GnomAD database, including 59,526 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 0.88 (59516 hom., cov: 33)
  • Exomes 𝑓: 0.88 (10 hom.)
• Consequence: TCF21 ENST00000237316.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.21
• Publications: 15 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000237316.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF21	NM_198392.3		c.*9-66G>A		intron	N/A	NP_938206.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF21	ENST00000237316.3	TSL:1	c.*9-66G>A		intron	N/A	ENSP00000237316.3
	TARID	ENST00000795402.1		n.151+23973C>T		intron	N/A
	TARID	ENST00000795414.1		n.208+23973C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134454 AN: 152188 Hom.: 59473 Cov.: 33

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.874

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.903

Gnomad OTH AF: 0.889

GnomAD4 exome AF: 0.885 AC: 23 AN: 26 Hom.: 10 Cov.: 0 AF XY: 0.875 AC XY: 21 AN XY: 24

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: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 16 AN: 16

Other (OTH) AF: 0.667 AC: 4 AN: 6

GnomAD4 genome AF: 0.883 AC: 134549 AN: 152306 Hom.: 59516 Cov.: 33 AF XY: 0.881 AC XY: 65641 AN XY: 74468

African (AFR) AF: 0.852 AC: 35386 AN: 41552

American (AMR) AF: 0.928 AC: 14202 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.874 AC: 3033 AN: 3472

East Asian (EAS) AF: 0.826 AC: 4277 AN: 5176

South Asian (SAS) AF: 0.853 AC: 4122 AN: 4832

European-Finnish (FIN) AF: 0.860 AC: 9120 AN: 10610

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.903 AC: 61456 AN: 68036

Other (OTH) AF: 0.886 AC: 1873 AN: 2114

Alfa AF: 0.882 Hom.: 25457

Bravo AF: 0.891

Asia WGS AF: 0.816 AC: 2841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	17
DANN	Benign	0.93
PhyloP100		3.2
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: rs2327433; hg19: chr6-134214227;