rs6001762

Positions:

• chr22-40099469-C-T

Variant summary

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

The ENST00000402203.5(TNRC6B):​c.-120-17586C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,934 control chromosomes in the GnomAD database, including 16,184 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 (16184 hom., cov: 31)
• Consequence: TNRC6B ENST00000402203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNRC6B	NM_001024843.2	c.-120-17586C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNRC6B	ENST00000402203.5	c.-120-17586C>T		intron_variant		1		A2
TNRC6B	ENST00000301923.13	c.-120-17586C>T		intron_variant		5		A2
TNRC6B	ENST00000441751.5	c.-120-17586C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56156 AN: 151816 Hom.: 16128 Cov.: 31

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.0301

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.370 AC: 56267 AN: 151934 Hom.: 16184 Cov.: 31 AF XY: 0.361 AC XY: 26825 AN XY: 74246

Gnomad4 AFR AF: 0.807

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.0299

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.301

Alfa AF: 0.230 Hom.: 6823

Bravo AF: 0.385

Asia WGS AF: 0.228 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.77
DANN	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6001762; hg19: chr22-40495473;