rs139911

Variant names:

• chr22-40308048-C-T
• rs139911
• NM_001162501.2:c.4121-464C>T

Variant summary

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

The NM_001162501.2(TNRC6B):​c.4121-464C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 152,064 control chromosomes in the GnomAD database, including 35,776 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 0.67 (35776 hom., cov: 31)
• Consequence: TNRC6B NM_001162501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC6B	NM_001162501.2	c.4121-464C>T		intron_variant	Intron 15 of 22	ENST00000454349.7	NP_001155973.1
TNRC6B	NM_015088.3	c.3791-464C>T		intron_variant	Intron 13 of 20		NP_055903.2
TNRC6B	NM_001024843.2	c.1709-464C>T		intron_variant	Intron 16 of 23		NP_001020014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000454349.7	c.4121-464C>T		intron_variant	Intron 15 of 22	2	NM_001162501.2	ENSP00000401946.2

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101304 AN: 151946 Hom.: 35701 Cov.: 31

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.737

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.667 AC: 101437 AN: 152064 Hom.: 35776 Cov.: 31 AF XY: 0.666 AC XY: 49508 AN XY: 74308

African (AFR) AF: 0.907 AC: 37655 AN: 41514

American (AMR) AF: 0.613 AC: 9361 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1890 AN: 3468

East Asian (EAS) AF: 0.433 AC: 2232 AN: 5158

South Asian (SAS) AF: 0.740 AC: 3558 AN: 4810

European-Finnish (FIN) AF: 0.587 AC: 6197 AN: 10556

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38578 AN: 67962

Other (OTH) AF: 0.588 AC: 1242 AN: 2112

Alfa AF: 0.588 Hom.: 11464

Bravo AF: 0.676

Asia WGS AF: 0.663 AC: 2307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.36
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs139911; hg19: chr22-40704052;