rs2072858

Positions:

• chr22-40312675-T-C

Variant summary

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

The NM_001162501.2(TNRC6B):​c.4582+24T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 1,601,200 control chromosomes in the GnomAD database, including 105,185 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 (8325 hom., cov: 32)
  • Exomes 𝑓: 0.36 (96860 hom.)
• Consequence: TNRC6B NM_001162501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNRC6B	NM_001162501.2	c.4582+24T>C		intron_variant		ENST00000454349.7	NP_001155973.1
TNRC6B	NM_001024843.2	c.2170+24T>C		intron_variant			NP_001020014.1
TNRC6B	NM_015088.3	c.4252+24T>C		intron_variant			NP_055903.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000454349.7	c.4582+24T>C		intron_variant		2	NM_001162501.2	ENSP00000401946	P3

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47688 AN: 151926 Hom.: 8316 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.304

GnomAD3 exomes AF: 0.389 AC: 93062 AN: 239282 Hom.: 19872 AF XY: 0.387 AC XY: 50182 AN XY: 129770

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.586

Gnomad ASJ exome AF: 0.304

Gnomad EAS exome AF: 0.417

Gnomad SAS exome AF: 0.458

Gnomad FIN exome AF: 0.394

Gnomad NFE exome AF: 0.346

Gnomad OTH exome AF: 0.367

GnomAD4 exome AF: 0.360 AC: 521409 AN: 1449156 Hom.: 96860 Cov.: 34 AF XY: 0.362 AC XY: 260788 AN XY: 719842

Gnomad4 AFR exome AF: 0.160

Gnomad4 AMR exome AF: 0.563

Gnomad4 ASJ exome AF: 0.307

Gnomad4 EAS exome AF: 0.447

Gnomad4 SAS exome AF: 0.453

Gnomad4 FIN exome AF: 0.390

Gnomad4 NFE exome AF: 0.349

Gnomad4 OTH exome AF: 0.338

GnomAD4 genome AF: 0.314 AC: 47718 AN: 152044 Hom.: 8325 Cov.: 32 AF XY: 0.323 AC XY: 23968 AN XY: 74318

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.306

Alfa AF: 0.349 Hom.: 5579

Bravo AF: 0.311

Asia WGS AF: 0.477 AC: 1658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.37

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: rs2072858; hg19: chr22-40708679; COSMIC: COSV57302867;