22-42274959-T-C

Position:

• chr22-42274959-T-C

Variant summary

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

The ENST00000359486.8(TCF20):​c.-37+8868A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,200 control chromosomes in the GnomAD database, including 11,207 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 0.35 (11196 hom., cov: 32)
  • Exomes 𝑓: 0.48 (11 hom.)
• Consequence: TCF20 ENST00000359486.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

Genes affected

TCF20 (HGNC:11631): (transcription factor 20) This gene encodes a transcription factor that recognizes the platelet-derived growth factor-responsive element in the matrix metalloproteinase 3 promoter. The encoded protein is thought to be a transcriptional coactivator, enhancing the activity of transcription factors such as JUN and SP1. Mutations in this gene are associated with autism spectrum disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

OGFRP1 (HGNC:50511): (opioid growth factor receptor pseudogene 1)

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 (SAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF20	NM_005650.4	c.-37+8868A>G		intron_variant
TCF20	XM_047441474.1	c.-36-59618A>G		intron_variant
TCF20	XM_047441476.1	c.-36-59618A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OGFRP1	ENST00000332965.4	n.1348T>C		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53672 AN: 151998 Hom.: 11181 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.377

GnomAD4 exome AF: 0.476 AC: 40 AN: 84 Hom.: 11 Cov.: 0 AF XY: 0.471 AC XY: 33 AN XY: 70

Gnomad4 AFR exome AF: 0.500

Gnomad4 NFE exome AF: 0.456

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.353 AC: 53687 AN: 152116 Hom.: 11196 Cov.: 32 AF XY: 0.357 AC XY: 26530 AN XY: 74368

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.384

Alfa AF: 0.390 Hom.: 2034

Bravo AF: 0.342

Asia WGS AF: 0.414 AC: 1438 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	0.28
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs134882; hg19: chr22-42670965;