chr22-40058065-T-G

Variant names:

• chr22-40058065-T-G
• rs7291691
• ENST00000402203.5:c.-121+12477T>G

Variant summary

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

The ENST00000402203.5(TNRC6B):​c.-121+12477T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,158 control chromosomes in the GnomAD database, including 15,112 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 0.37 (15112 hom., cov: 32)
• Consequence: TNRC6B ENST00000402203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313
• Publications: 13 publications found

Genes affected

TNRC6B (HGNC:29190): (trinucleotide repeat containing adaptor 6B) Enables RNA binding activity. Involved in regulation of gene expression. Predicted to be located in cytosol. Predicted to be active in P-body and nucleoplasm. Implicated in subserous uterine fibroid and uterine fibroid. [provided by Alliance of Genome Resources, Apr 2022]

TNRC6B Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• global developmental delay with speech and behavioral abnormalities

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC6B	NM_001024843.2	c.-121+13067T>G		intron_variant	Intron 1 of 23		NP_001020014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000402203.5	c.-121+12477T>G		intron_variant	Intron 1 of 23	1		ENSP00000384795.1
TNRC6B	ENST00000301923.13	c.-121+13067T>G		intron_variant	Intron 1 of 23	5		ENSP00000306759.9

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55923 AN: 152040 Hom.: 15059 Cov.: 32

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.0300

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.368 AC: 56028 AN: 152158 Hom.: 15112 Cov.: 32 AF XY: 0.359 AC XY: 26700 AN XY: 74410

African (AFR) AF: 0.766 AC: 31749 AN: 41468

American (AMR) AF: 0.214 AC: 3280 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 826 AN: 3466

East Asian (EAS) AF: 0.0299 AC: 155 AN: 5188

South Asian (SAS) AF: 0.319 AC: 1542 AN: 4830

European-Finnish (FIN) AF: 0.194 AC: 2059 AN: 10606

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15324 AN: 67994

Other (OTH) AF: 0.312 AC: 659 AN: 2112

Alfa AF: 0.259 Hom.: 8196

Bravo AF: 0.383

Asia WGS AF: 0.235 AC: 820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.53
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7291691; hg19: chr22-40454069;