rs17478227

Variant names:

• chr22-42258321-C-G
• rs17478227
• NM_001378418.1:c.-37+12018G>C

Variant summary

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

The NM_001378418.1(TCF20):​c.-37+12018G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,084 control chromosomes in the GnomAD database, including 1,634 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 0.13 (1634 hom., cov: 32)
• Consequence: TCF20 NM_001378418.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266
• Publications: 7 publications found

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]

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378418.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF20	NM_001378418.1	MANE Select	c.-37+12018G>C		intron	N/A	NP_001365347.1
	TCF20	NM_005650.4		c.-37+25506G>C		intron	N/A	NP_005641.1
	TCF20	NM_181492.3		c.-37+12018G>C		intron	N/A	NP_852469.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF20	ENST00000677622.1	MANE Select	c.-37+12018G>C		intron	N/A	ENSP00000503828.1
	TCF20	ENST00000359486.8	TSL:1	c.-37+25506G>C		intron	N/A	ENSP00000352463.3
	TCF20	ENST00000683686.1		c.-37+9992G>C		intron	N/A	ENSP00000508272.1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19018 AN: 151966 Hom.: 1634 Cov.: 32

Gnomad AFR AF: 0.0379

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.0994

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.0872

Gnomad FIN AF: 0.0958

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.125 AC: 19012 AN: 152084 Hom.: 1634 Cov.: 32 AF XY: 0.118 AC XY: 8768 AN XY: 74352

African (AFR) AF: 0.0378 AC: 1566 AN: 41472

American (AMR) AF: 0.0993 AC: 1517 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 718 AN: 3462

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5176

South Asian (SAS) AF: 0.0867 AC: 418 AN: 4822

European-Finnish (FIN) AF: 0.0958 AC: 1013 AN: 10578

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.195 AC: 13242 AN: 67988

Other (OTH) AF: 0.124 AC: 262 AN: 2112

Alfa AF: 0.157 Hom.: 264

Bravo AF: 0.121

Asia WGS AF: 0.0540 AC: 191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.0
DANN	Benign	0.79
PhyloP100		0.27

Splicing

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

Other links and lift over

dbSNP: rs17478227; hg19: chr22-42654327;