rs4821941

Variant names:

• chr22-40279087-A-G
• rs4821941
• NM_001162501.2:c.3263-908A>G

Variant summary

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

The NM_001162501.2(TNRC6B):​c.3263-908A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,016 control chromosomes in the GnomAD database, including 8,237 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 0.31 (8237 hom., cov: 32)
• Consequence: TNRC6B NM_001162501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172
• Publications: 10 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC6B	NM_001162501.2	c.3263-908A>G		intron_variant	Intron 9 of 22	ENST00000454349.7	NP_001155973.1
TNRC6B	NM_015088.3	c.3104-908A>G		intron_variant	Intron 8 of 20		NP_055903.2
TNRC6B	NM_001024843.2	c.1022-908A>G		intron_variant	Intron 11 of 23		NP_001020014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000454349.7	c.3263-908A>G		intron_variant	Intron 9 of 22	2	NM_001162501.2	ENSP00000401946.2

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47644 AN: 151898 Hom.: 8227 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.314 AC: 47675 AN: 152016 Hom.: 8237 Cov.: 32 AF XY: 0.322 AC XY: 23898 AN XY: 74324

African (AFR) AF: 0.182 AC: 7538 AN: 41456

American (AMR) AF: 0.422 AC: 6436 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1039 AN: 3468

East Asian (EAS) AF: 0.420 AC: 2169 AN: 5164

South Asian (SAS) AF: 0.460 AC: 2219 AN: 4826

European-Finnish (FIN) AF: 0.383 AC: 4046 AN: 10566

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.341 AC: 23144 AN: 67962

Other (OTH) AF: 0.309 AC: 651 AN: 2108

Alfa AF: 0.333 Hom.: 17225

Bravo AF: 0.312

Asia WGS AF: 0.474 AC: 1647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.9
DANN	Benign	0.61
PhyloP100		0.17
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: rs4821941; hg19: chr22-40675091;