18-55586153-G-GAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_001083962.2(TCF4):​c.73-837_73-802dupGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00097 ( 3 hom., cov: 0)
Exomes 𝑓: 0.0015 ( 76 hom. )
Failed GnomAD Quality Control

Consequence

TCF4
NM_001083962.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000974 (132/135540) while in subpopulation EAS AF= 0.0016 (7/4382). AF 95% confidence interval is 0.00078. There are 3 homozygotes in gnomad4. There are 67 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
High AC in GnomAd4 at 132 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TCF4NM_001083962.2 linkc.73-837_73-802dupGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT intron_variant Intron 2 of 19 ENST00000354452.8 NP_001077431.1 P15884-3B3KVA4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TCF4ENST00000354452.8 linkc.73-837_73-802dupGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT intron_variant Intron 2 of 19 5 NM_001083962.2 ENSP00000346440.3 P15884-3

Frequencies

GnomAD3 genomes
AF:
0.000975
AC:
132
AN:
135448
Hom.:
3
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.000692
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00124
Gnomad ASJ
AF:
0.00126
Gnomad EAS
AF:
0.00159
Gnomad SAS
AF:
0.00125
Gnomad FIN
AF:
0.00121
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000979
Gnomad OTH
AF:
0.00162
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00149
AC:
854
AN:
572478
Hom.:
76
Cov.:
0
AF XY:
0.00154
AC XY:
460
AN XY:
299082
show subpopulations
Gnomad4 AFR exome
AF:
0.000610
Gnomad4 AMR exome
AF:
0.00177
Gnomad4 ASJ exome
AF:
0.00195
Gnomad4 EAS exome
AF:
0.00241
Gnomad4 SAS exome
AF:
0.00160
Gnomad4 FIN exome
AF:
0.00205
Gnomad4 NFE exome
AF:
0.00141
Gnomad4 OTH exome
AF:
0.00130
GnomAD4 genome
AF:
0.000974
AC:
132
AN:
135540
Hom.:
3
Cov.:
0
AF XY:
0.00102
AC XY:
67
AN XY:
65550
show subpopulations
Gnomad4 AFR
AF:
0.000690
Gnomad4 AMR
AF:
0.00124
Gnomad4 ASJ
AF:
0.00126
Gnomad4 EAS
AF:
0.00160
Gnomad4 SAS
AF:
0.00125
Gnomad4 FIN
AF:
0.00121
Gnomad4 NFE
AF:
0.000979
Gnomad4 OTH
AF:
0.00160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs55725917; hg19: chr18-53253384; API