rs470113

Positions:

• chr22-40333610-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001162501.2(TNRC6B):​c.*10369A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,526 control chromosomes in the GnomAD database, including 3,557 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 0.20 (3545 hom., cov: 31)
  • Exomes 𝑓: 0.21 (12 hom.)
• Consequence: TNRC6B NM_001162501.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNRC6B	NM_001162501.2	c.*10369A>G		3_prime_UTR_variant	23/23	ENST00000454349.7	NP_001155973.1
TNRC6B	NM_001024843.2	c.*10369A>G		3_prime_UTR_variant	24/24		NP_001020014.1
TNRC6B	NM_015088.3	c.*10369A>G		3_prime_UTR_variant	21/21		NP_055903.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000454349.7	c.*10369A>G		3_prime_UTR_variant	23/23	2	NM_001162501.2	ENSP00000401946	P3
TNRC6B	ENST00000335727.13	c.*10369A>G		3_prime_UTR_variant	21/21	1		ENSP00000338371
TNRC6B	ENST00000301923.13	c.*10369A>G		3_prime_UTR_variant	24/24	5		ENSP00000306759	A2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30150 AN: 151994 Hom.: 3534 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.215 AC: 89 AN: 414 Hom.: 12 Cov.: 0 AF XY: 0.224 AC XY: 55 AN XY: 246

Gnomad4 FIN exome AF: 0.220

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.198 AC: 30192 AN: 152112 Hom.: 3545 Cov.: 31 AF XY: 0.204 AC XY: 15189 AN XY: 74322

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.184

Alfa AF: 0.188 Hom.: 6881

Bravo AF: 0.213

Asia WGS AF: 0.215 AC: 749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.39
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs470113; hg19: chr22-40729614; COSMIC: COSV57308937;