rs282163

chr20-607445-A-Cchr20-607445-A-Gchr20-607445-A-T

Variant summary

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

The NM_004609.4(TCF15):c.525+2268T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 152,166 control chromosomes in the GnomAD database, including 50,126 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 0.81 (50126 hom., cov: 33)
• Consequence: TCF15 NM_004609.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167

Genes affected

TCF15 (HGNC:11627): (transcription factor 15) The protein encoded by this gene is found in the nucleus and may be involved in the early transcriptional regulation of patterning of the mesoderm. The encoded basic helix-loop-helix protein requires dimerization with another basic helix-loop-helix protein for efficient DNA binding. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF15	NM_004609.4	c.525+2268T>G		intron_variant		ENST00000246080.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF15	ENST00000246080.4	c.525+2268T>G		intron_variant		1	NM_004609.4	P1

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123147 AN: 152050 Hom.: 50079 Cov.: 33

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.811

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

GnomAD4 genome AF: 0.810 AC: 123251 AN: 152166 Hom.: 50126 Cov.: 33 AF XY: 0.815 AC XY: 60654 AN XY: 74394

Gnomad4 AFR AF: 0.772

Gnomad4 AMR AF: 0.862

Gnomad4 ASJ AF: 0.820

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.908

Gnomad4 FIN AF: 0.840

Gnomad4 NFE AF: 0.794

Gnomad4 OTH AF: 0.814

Alfa AF: 0.803 Hom.: 26121

Bravo AF: 0.811

Asia WGS AF: 0.944 AC: 3282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.5
Dann	Benign	0.82

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: rs282163; hg19: chr20-588089;