15-56920030-TTTTGTTTG-TTTTGTTTGTTTG

Variant names:

• chr15-56920030-T-TTTTG
• rs527665020
• NM_207037.2:c.75+62_75+65dupGTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_207037.2(TCF12):​c.75+62_75+65dupGTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00612 in 1,605,772 control chromosomes in the GnomAD database, including 37 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0040 (1 hom., cov: 30)
  • Exomes 𝑓: 0.0063 (36 hom.)
• Consequence: TCF12 NM_207037.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54

Genes affected

TCF12 (HGNC:11623): (transcription factor 12) The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH) E-protein family that recognizes the consensus binding site (E-box) CANNTG. This encoded protein is expressed in many tissues, among them skeletal muscle, thymus, B- and T-cells, and may participate in regulating lineage-specific gene expression through the formation of heterodimers with other bHLH E-proteins. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00399 (606/151940) while in subpopulation NFE AF= 0.00645 (438/67928). AF 95% confidence interval is 0.00595. There are 1 homozygotes in gnomad4. There are 277 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 606 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF12	NM_207037.2	c.75+62_75+65dupGTTT		intron_variant	Intron 2 of 20	ENST00000333725.10	NP_996920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF12	ENST00000333725.10	c.75+42_75+43insTTTG		intron_variant	Intron 2 of 20	1	NM_207037.2	ENSP00000331057.6

Frequencies

GnomAD3 genomes AF: 0.00399 AC: 606 AN: 151822 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00779

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000834

Gnomad FIN AF: 0.000945

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00645

Gnomad OTH AF: 0.00384

GnomAD3 exomes AF: 0.00423 AC: 1044 AN: 246558 Hom.: 7 AF XY: 0.00420 AC XY: 560 AN XY: 133210

Gnomad AFR exome AF: 0.00138

Gnomad AMR exome AF: 0.00281

Gnomad ASJ exome AF: 0.00715

Gnomad EAS exome AF: 0.0000553

Gnomad SAS exome AF: 0.000729

Gnomad FIN exome AF: 0.00215

Gnomad NFE exome AF: 0.00692

Gnomad OTH exome AF: 0.00300

GnomAD4 exome AF: 0.00634 AC: 9216 AN: 1453832 Hom.: 36 Cov.: 26 AF XY: 0.00632 AC XY: 4576 AN XY: 723690

Gnomad4 AFR exome AF: 0.00156

Gnomad4 AMR exome AF: 0.00333

Gnomad4 ASJ exome AF: 0.00852

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000767

Gnomad4 FIN exome AF: 0.00194

Gnomad4 NFE exome AF: 0.00750

Gnomad4 OTH exome AF: 0.00537

GnomAD4 genome AF: 0.00399 AC: 606 AN: 151940 Hom.: 1 Cov.: 30 AF XY: 0.00373 AC XY: 277 AN XY: 74252

Gnomad4 AFR AF: 0.00186

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.00779

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000834

Gnomad4 FIN AF: 0.000945

Gnomad4 NFE AF: 0.00645

Gnomad4 OTH AF: 0.00380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs527665020; hg19: chr15-57212228;