rs7235757

Variant names:

• chr18-55400723-G-A
• rs7235757
• NM_001083962.2:c.369+2731C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-55400723-G-A
• chr18-55400723-G-C
• chr18-55400723-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.369+2731C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 206,642 control chromosomes in the GnomAD database, including 19,077 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 0.42 (15276 hom., cov: 31)
  • Exomes 𝑓: 0.36 (3801 hom.)
• Consequence: TCF4 NM_001083962.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.743

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF4	NM_001083962.2	c.369+2731C>T		intron_variant	Intron 6 of 19	ENST00000354452.8	NP_001077431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF4	ENST00000354452.8	c.369+2731C>T		intron_variant	Intron 6 of 19	5	NM_001083962.2	ENSP00000346440.3

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63837 AN: 151766 Hom.: 15224 Cov.: 31

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.415

GnomAD4 exome AF: 0.357 AC: 19566 AN: 54758 Hom.: 3801 AF XY: 0.357 AC XY: 10531 AN XY: 29494

Gnomad4 AFR exome AF: 0.682

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.391

Gnomad4 EAS exome AF: 0.517

Gnomad4 SAS exome AF: 0.338

Gnomad4 FIN exome AF: 0.248

Gnomad4 NFE exome AF: 0.319

Gnomad4 OTH exome AF: 0.340

GnomAD4 genome AF: 0.421 AC: 63933 AN: 151884 Hom.: 15276 Cov.: 31 AF XY: 0.420 AC XY: 31183 AN XY: 74196

Gnomad4 AFR AF: 0.661

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.412

Alfa AF: 0.327 Hom.: 11192

Bravo AF: 0.443

Asia WGS AF: 0.409 AC: 1425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.0
DANN	Benign	0.39

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: rs7235757; hg19: chr18-53067954;