rs4821940

Variant names:

• chr22-40263569-T-C
• rs4821940
• NM_001162501.2:c.458-1119T>C

Your query was ambiguous. Multiple possible variants found:

• chr22-40263569-T-C
• chr22-40263569-T-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.458-1119T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,088 control chromosomes in the GnomAD database, including 17,346 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 0.46 (17346 hom., cov: 32)
• Consequence: TNRC6B NM_001162501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215
• Publications: 17 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

ENSG00000309895 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC6B	NM_001162501.2	c.458-1119T>C		intron_variant	Intron 4 of 22	ENST00000454349.7	NP_001155973.1
TNRC6B	NM_015088.3	c.458-1119T>C		intron_variant	Intron 4 of 20		NP_055903.2
TNRC6B	NM_001024843.2	c.565+1396T>C		intron_variant	Intron 7 of 23		NP_001020014.1
LOC124905121	XR_007068107.1	n.304-3201A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000454349.7	c.458-1119T>C		intron_variant	Intron 4 of 22	2	NM_001162501.2	ENSP00000401946.2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69322 AN: 151970 Hom.: 17332 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.456 AC: 69353 AN: 152088 Hom.: 17346 Cov.: 32 AF XY: 0.460 AC XY: 34168 AN XY: 74348

African (AFR) AF: 0.246 AC: 10217 AN: 41496

American (AMR) AF: 0.537 AC: 8203 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1750 AN: 3468

East Asian (EAS) AF: 0.426 AC: 2206 AN: 5174

South Asian (SAS) AF: 0.725 AC: 3498 AN: 4824

European-Finnish (FIN) AF: 0.510 AC: 5384 AN: 10562

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.537 AC: 36521 AN: 67978

Other (OTH) AF: 0.450 AC: 948 AN: 2108

Alfa AF: 0.520 Hom.: 13759

Bravo AF: 0.447

Asia WGS AF: 0.594 AC: 2067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.8
DANN	Benign	0.70
PhyloP100		-0.21
Mutation Taster		=99/1	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: rs4821940; hg19: chr22-40659573;