rs138039

Positions:

• chr22-40225284-G-A
• chr22-40225284-G-T

Variant summary

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

The NM_001162501.2(TNRC6B):​c.6-20731G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,012 control chromosomes in the GnomAD database, including 9,577 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 0.32 (9577 hom., cov: 32)
• Consequence: TNRC6B NM_001162501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNRC6B	NM_001162501.2	c.6-20731G>A		intron_variant		ENST00000454349.7
TNRC6B	NM_001024843.2	c.114-20731G>A		intron_variant
TNRC6B	NM_015088.3	c.6-20731G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNRC6B	ENST00000454349.7	c.6-20731G>A		intron_variant		2	NM_001162501.2	P3

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48745 AN: 151892 Hom.: 9575 Cov.: 32

Gnomad AFR AF: 0.0954

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.321 AC: 48744 AN: 152012 Hom.: 9577 Cov.: 32 AF XY: 0.323 AC XY: 23982 AN XY: 74280

Gnomad4 AFR AF: 0.0954

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.396

Alfa AF: 0.376 Hom.: 5860

Bravo AF: 0.311

Asia WGS AF: 0.343 AC: 1192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.0
DANN	Benign	0.28

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: rs138039; hg19: chr22-40621288;