rs2327430

Variant names:

• chr6-133888899-C-T
• rs2327430
• ENST00000607033.5:n.84G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-133888899-C-T
• chr6-133888899-C-A
• chr6-133888899-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000607033.5(TARID):​n.84G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 177,714 control chromosomes in the GnomAD database, including 34,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (28638 hom., cov: 32)
  • Exomes 𝑓: 0.67 (6068 hom.)
• Consequence: TARID ENST00000607033.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.468
• Publications: 7 publications found

Genes affected

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

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]

TCF21 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 6-133888899-C-T is Benign according to our data. Variant chr6-133888899-C-T is described in ClinVar as Benign. ClinVar VariationId is 1278224.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000607033.5. 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
	TARID	NR_109982.1		n.108G>A		non_coding_transcript_exon	Exon 1 of 9
	TCF21	NM_003206.4	MANE Select	c.-499C>T		upstream_gene	N/A	NP_003197.2
	TCF21	NM_198392.3		c.-499C>T		upstream_gene	N/A	NP_938206.1	O43680

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TARID	ENST00000607033.5	TSL:1	n.84G>A		non_coding_transcript_exon	Exon 1 of 9
	TARID	ENST00000607641.3	TSL:1	n.1430G>A		non_coding_transcript_exon	Exon 2 of 3
	TARID	ENST00000630728.1	TSL:1	n.1648G>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91141 AN: 151940 Hom.: 28620 Cov.: 32

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.612

GnomAD4 exome AF: 0.669 AC: 17152 AN: 25654 Hom.: 6068 Cov.: 0 AF XY: 0.673 AC XY: 8859 AN XY: 13156

African (AFR) AF: 0.424 AC: 174 AN: 410

American (AMR) AF: 0.775 AC: 2442 AN: 3152

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 190 AN: 316

East Asian (EAS) AF: 0.934 AC: 1406 AN: 1506

South Asian (SAS) AF: 0.728 AC: 2214 AN: 3042

European-Finnish (FIN) AF: 0.493 AC: 364 AN: 738

Middle Eastern (MID) AF: 0.568 AC: 42 AN: 74

European-Non Finnish (NFE) AF: 0.631 AC: 9565 AN: 15170

Other (OTH) AF: 0.606 AC: 755 AN: 1246

GnomAD4 genome AF: 0.600 AC: 91201 AN: 152060 Hom.: 28638 Cov.: 32 AF XY: 0.600 AC XY: 44560 AN XY: 74326

African (AFR) AF: 0.430 AC: 17826 AN: 41460

American (AMR) AF: 0.729 AC: 11152 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2225 AN: 3466

East Asian (EAS) AF: 0.926 AC: 4798 AN: 5180

South Asian (SAS) AF: 0.715 AC: 3441 AN: 4814

European-Finnish (FIN) AF: 0.500 AC: 5275 AN: 10560

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.653 AC: 44376 AN: 67972

Other (OTH) AF: 0.615 AC: 1300 AN: 2114

Alfa AF: 0.651 Hom.: 54184

Bravo AF: 0.612

Asia WGS AF: 0.764 AC: 2656 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.4
DANN	Benign	0.59
PhyloP100		-0.47
PromoterAI		0.055	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2327430; hg19: chr6-134210037; COSMIC: COSV52819538;