rs9623117

Positions:

• chr22-40056115-T-C

Variant summary

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

The ENST00000402203.5(TNRC6B):​c.-121+10527T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,086 control chromosomes in the GnomAD database, including 15,089 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 0.37 (15089 hom., cov: 32)
• Consequence: TNRC6B ENST00000402203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNRC6B	NM_001024843.2	c.-121+11117T>C		intron_variant			NP_001020014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000402203.5	c.-121+10527T>C		intron_variant		1		ENSP00000384795	A2
TNRC6B	ENST00000301923.13	c.-121+11117T>C		intron_variant		5		ENSP00000306759	A2
TNRC6B	ENST00000441751.5	c.-121+11117T>C		intron_variant		5		ENSP00000397491

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55852 AN: 151968 Hom.: 15035 Cov.: 32

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.0300

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.368 AC: 55958 AN: 152086 Hom.: 15089 Cov.: 32 AF XY: 0.358 AC XY: 26651 AN XY: 74356

Gnomad4 AFR AF: 0.765

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.0299

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.312

Alfa AF: 0.233 Hom.: 7610

Bravo AF: 0.383

Asia WGS AF: 0.235 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.19
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9623117; hg19: chr22-40452119; COSMIC: COSV57289779;