rs2899334

Positions:

• chr22-40155846-T-C

Variant summary

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

The ENST00000402203.5(TNRC6B):​c.46-269T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,140 control chromosomes in the GnomAD database, including 36,798 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 0.68 (36798 hom., cov: 33)
• Consequence: TNRC6B ENST00000402203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNRC6B	NM_001024843.2	c.46-269T>C		intron_variant			NP_001020014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000402203.5	c.46-269T>C		intron_variant		1		ENSP00000384795	A2
TNRC6B	ENST00000301923.13	c.46-269T>C		intron_variant		5		ENSP00000306759	A2
TNRC6B	ENST00000441751.5	c.46-269T>C		intron_variant		5		ENSP00000397491

Frequencies

GnomAD3 genomes AF: 0.678 AC: 103113 AN: 152022 Hom.: 36733 Cov.: 33

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.679 AC: 103235 AN: 152140 Hom.: 36798 Cov.: 33 AF XY: 0.676 AC XY: 50291 AN XY: 74364

Gnomad4 AFR AF: 0.904

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.589

Gnomad4 OTH AF: 0.605

Alfa AF: 0.658 Hom.: 4880

Bravo AF: 0.688

Asia WGS AF: 0.656 AC: 2281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.4
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2899334; hg19: chr22-40551850;