rs134882

Variant names:

• chr22-42274959-T-C
• rs134882
• ENST00000332965.4:n.1348T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000332965.4(OGFRP1):​n.1348T>C variant causes a non coding transcript exon 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: OGFRP1 ENST00000332965.4 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 14 publications found

Genes affected

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

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]

TCF20 Gene-Disease associations (from GenCC):

• developmental delay with variable intellectual impairment and behavioral abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Illumina
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TCF20	NM_005650.4	c.-37+8868A>G		intron_variant	Intron 1 of 5		NP_005641.1
TCF20	XM_047441474.1	c.-36-59618A>G		intron_variant	Intron 1 of 5		XP_047297430.1
TCF20	XM_047441476.1	c.-36-59618A>G		intron_variant	Intron 1 of 4		XP_047297432.1
OGFRP1	NR_036498.1	n.*97T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OGFRP1	ENST00000332965.4	n.1348T>C		non_coding_transcript_exon_variant	Exon 2 of 2	1
TCF20	ENST00000359486.8	c.-37+8868A>G		intron_variant	Intron 1 of 5	1		ENSP00000352463.3
TCF20	ENST00000675876.1	c.-37+43105A>G		intron_variant	Intron 1 of 1			ENSP00000502259.1

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.456 AC: 31 AN: 68

Other (OTH) AF: 0.667 AC: 8 AN: 12

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

African (AFR) AF: 0.121 AC: 5038 AN: 41522

American (AMR) AF: 0.439 AC: 6706 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1280 AN: 3470

East Asian (EAS) AF: 0.324 AC: 1677 AN: 5176

South Asian (SAS) AF: 0.472 AC: 2273 AN: 4818

European-Finnish (FIN) AF: 0.449 AC: 4742 AN: 10568

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30741 AN: 67958

Other (OTH) AF: 0.384 AC: 811 AN: 2114

Alfa AF: 0.406 Hom.: 20185

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
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs134882; hg19: chr22-42670965;