18-55586153-GAGCAGCAGCAGCAGC-G

Variant names:

• chr18-55586153-GAGCAGCAGCAGCAGC-G
• rs55725917
• NM_001083962.2:c.73-816_73-802delGCTGCTGCTGCTGCT

Variant summary

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

The NM_001083962.2(TCF4):​c.73-816_73-802delGCTGCTGCTGCTGCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00437 in 707,772 control chromosomes in the GnomAD database, including 100 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.013 (43 hom., cov: 0)
  • Exomes 𝑓: 0.0024 (57 hom.)
• Consequence: TCF4 NM_001083962.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.885

Genes affected

TCF4 (HGNC:11634): (transcription factor 4) This gene encodes transcription factor 4, a basic helix-loop-helix transcription factor. The encoded protein recognizes an Ephrussi-box ('E-box') binding site ('CANNTG') - a motif first identified in immunoglobulin enhancers. This gene is broadly expressed, and may play an important role in nervous system development. Defects in this gene are a cause of Pitt-Hopkins syndrome. In addition, an intronic CTG repeat normally numbering 10-37 repeat units can expand to >50 repeat units and cause Fuchs endothelial corneal dystrophy. Multiple alternatively spliced transcript variants that encode different proteins have been described. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1702/135496) while in subpopulation AFR AF= 0.0392 (1475/37622). AF 95% confidence interval is 0.0375. There are 43 homozygotes in gnomad4. There are 799 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1702 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF4	NM_001083962.2	c.73-816_73-802delGCTGCTGCTGCTGCT		intron_variant	Intron 2 of 19	ENST00000354452.8	NP_001077431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF4	ENST00000354452.8	c.73-816_73-802delGCTGCTGCTGCTGCT		intron_variant	Intron 2 of 19	5	NM_001083962.2	ENSP00000346440.3

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1697 AN: 135404 Hom.: 42 Cov.: 0

Gnomad AFR AF: 0.0392

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00642

Gnomad ASJ AF: 0.00315

Gnomad EAS AF: 0.00273

Gnomad SAS AF: 0.00602

Gnomad FIN AF: 0.000329

Gnomad MID AF: 0.0132

Gnomad NFE AF: 0.00122

Gnomad OTH AF: 0.00862

GnomAD4 exome AF: 0.00243 AC: 1392 AN: 572276 Hom.: 57 AF XY: 0.00241 AC XY: 722 AN XY: 298988

Gnomad4 AFR exome AF: 0.0270

Gnomad4 AMR exome AF: 0.00250

Gnomad4 ASJ exome AF: 0.00275

Gnomad4 EAS exome AF: 0.00462

Gnomad4 SAS exome AF: 0.00314

Gnomad4 FIN exome AF: 0.00103

Gnomad4 NFE exome AF: 0.000936

Gnomad4 OTH exome AF: 0.00494

GnomAD4 genome AF: 0.0126 AC: 1702 AN: 135496 Hom.: 43 Cov.: 0 AF XY: 0.0122 AC XY: 799 AN XY: 65528

Gnomad4 AFR AF: 0.0392

Gnomad4 AMR AF: 0.00641

Gnomad4 ASJ AF: 0.00315

Gnomad4 EAS AF: 0.00274

Gnomad4 SAS AF: 0.00627

Gnomad4 FIN AF: 0.000329

Gnomad4 NFE AF: 0.00122

Gnomad4 OTH AF: 0.00800

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: rs55725917; hg19: chr18-53253384;