22-40112718-T-C

Position:

• chr22-40112718-T-C

Variant summary

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

The ENST00000402203.5(TNRC6B):​c.-120-4337T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0572 in 152,308 control chromosomes in the GnomAD database, including 795 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 0.057 (795 hom., cov: 32)
• Consequence: TNRC6B ENST00000402203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNRC6B	NM_001024843.2	c.-120-4337T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNRC6B	ENST00000402203.5	c.-120-4337T>C		intron_variant		1		A2
TNRC6B	ENST00000301923.13	c.-120-4337T>C		intron_variant		5		A2
TNRC6B	ENST00000441751.5	c.-120-4337T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0571 AC: 8691 AN: 152190 Hom.: 791 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0268

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00351

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00259

Gnomad OTH AF: 0.0406

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

GnomAD4 genome AF: 0.0572 AC: 8712 AN: 152308 Hom.: 795 Cov.: 32 AF XY: 0.0557 AC XY: 4150 AN XY: 74492

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.0267

Gnomad4 ASJ AF: 0.0233

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00259

Gnomad4 OTH AF: 0.0407

Alfa AF: 0.0277 Hom.: 63

Bravo AF: 0.0646

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10483202; hg19: chr22-40508722;