chr18-55543071-G-T

Position:

• chr18-55543071-G-T

Variant summary

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

The NM_001083962.2(TCF4):​c.145+42209C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 152,058 control chromosomes in the GnomAD database, including 59,685 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 0.88 (59685 hom., cov: 32)
• Consequence: TCF4 NM_001083962.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301

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]

TCF4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF4	NM_001083962.2	c.145+42209C>A		intron_variant		ENST00000354452.8	NP_001077431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF4	ENST00000354452.8	c.145+42209C>A		intron_variant		5	NM_001083962.2	ENSP00000346440.3

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134232 AN: 151940 Hom.: 59620 Cov.: 32

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.905

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.875

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.878

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

GnomAD4 genome AF: 0.884 AC: 134354 AN: 152058 Hom.: 59685 Cov.: 32 AF XY: 0.886 AC XY: 65841 AN XY: 74348

Gnomad4 AFR AF: 0.970

Gnomad4 AMR AF: 0.905

Gnomad4 ASJ AF: 0.757

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.874

Gnomad4 FIN AF: 0.848

Gnomad4 NFE AF: 0.833

Gnomad4 OTH AF: 0.879

Alfa AF: 0.840 Hom.: 77152

Bravo AF: 0.892

Asia WGS AF: 0.956 AC: 3321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.58
DANN	Benign	0.28

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: rs613872; hg19: chr18-53210302;