chr22-40099469-C-T

Variant names:

• chr22-40099469-C-T
• rs6001762
• ENST00000402203.5:c.-120-17586C>T

Variant summary

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

The ENST00000402203.5(TNRC6B):​c.-120-17586C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,934 control chromosomes in the GnomAD database, including 16,184 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 (16184 hom., cov: 31)
• Consequence: TNRC6B ENST00000402203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000402203.5. 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
	TNRC6B	NM_001024843.2		c.-120-17586C>T		intron	N/A	NP_001020014.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC6B	ENST00000402203.5	TSL:1	c.-120-17586C>T		intron	N/A	ENSP00000384795.1
	TNRC6B	ENST00000301923.13	TSL:5	c.-120-17586C>T		intron	N/A	ENSP00000306759.9

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56156 AN: 151816 Hom.: 16128 Cov.: 31

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.0301

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.370 AC: 56267 AN: 151934 Hom.: 16184 Cov.: 31 AF XY: 0.361 AC XY: 26825 AN XY: 74246

African (AFR) AF: 0.807 AC: 33433 AN: 41422

American (AMR) AF: 0.203 AC: 3094 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 781 AN: 3464

East Asian (EAS) AF: 0.0299 AC: 155 AN: 5178

South Asian (SAS) AF: 0.307 AC: 1478 AN: 4810

European-Finnish (FIN) AF: 0.192 AC: 2025 AN: 10520

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14300 AN: 67962

Other (OTH) AF: 0.301 AC: 635 AN: 2110

Alfa AF: 0.244 Hom.: 18236

Bravo AF: 0.385

Asia WGS AF: 0.228 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.77
DANN	Benign	0.30
PhyloP100		-0.20
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: rs6001762; hg19: chr22-40495473;