6-133891457-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003206.4(TCF21):c.451-256A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 152,250 control chromosomes in the GnomAD database, including 57,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.87 (57685 hom., cov: 33)
• Consequence: TCF21 NM_003206.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0840

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-133891457-A-G is Benign according to our data. Variant chr6-133891457-A-G is described in ClinVar as [Benign]. Clinvar id is 1183604.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF21	NM_003206.4	c.451-256A>G		intron_variant		ENST00000367882.5
TCF21	NM_198392.3	c.451-256A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF21	ENST00000367882.5	c.451-256A>G		intron_variant		1	NM_003206.4	P1

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132214 AN: 152132 Hom.: 57651 Cov.: 33

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.881

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.869 AC: 132298 AN: 152250 Hom.: 57685 Cov.: 33 AF XY: 0.870 AC XY: 64783 AN XY: 74426

Gnomad4 AFR AF: 0.778

Gnomad4 AMR AF: 0.917

Gnomad4 ASJ AF: 0.882

Gnomad4 EAS AF: 0.874

Gnomad4 SAS AF: 0.906

Gnomad4 FIN AF: 0.895

Gnomad4 NFE AF: 0.905

Gnomad4 OTH AF: 0.878

Alfa AF: 0.875 Hom.: 7267

Bravo AF: 0.869

Asia WGS AF: 0.860 AC: 2994 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	8.7
Dann	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs9402546; hg19: chr6-134212595;