rs9320010

Positions:

• chr18-55386666-A-G
• chr18-55386666-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001083962.2(TCF4):​c.369+16788T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 152,040 control chromosomes in the GnomAD database, including 19,384 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (19384 hom., cov: 32)
• Consequence: TCF4 NM_001083962.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF4	NM_001083962.2	c.369+16788T>C		intron_variant		ENST00000354452.8	NP_001077431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF4	ENST00000354452.8	c.369+16788T>C		intron_variant		5	NM_001083962.2	ENSP00000346440	P3

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73983 AN: 151920 Hom.: 19349 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.487 AC: 74059 AN: 152040 Hom.: 19384 Cov.: 32 AF XY: 0.486 AC XY: 36141 AN XY: 74334

Gnomad4 AFR AF: 0.707

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.476

Alfa AF: 0.444 Hom.: 3372

Bravo AF: 0.508

Asia WGS AF: 0.423 AC: 1474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.28
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs9320010; hg19: chr18-53053897;