22-40258272-T-C

Position:

• chr22-40258272-T-C

Variant summary

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

The NM_001162501.2(TNRC6B):​c.116-3560T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 151,534 control chromosomes in the GnomAD database, including 8,301 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 (8301 hom., cov: 30)
• Consequence: TNRC6B NM_001162501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNRC6B	NM_001162501.2	c.116-3560T>C		intron_variant		ENST00000454349.7	NP_001155973.1
TNRC6B	NM_015088.3	c.116-3560T>C		intron_variant			NP_055903.2
TNRC6B	NM_001024843.2	c.224-3560T>C		intron_variant			NP_001020014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000454349.7	c.116-3560T>C		intron_variant		2	NM_001162501.2	ENSP00000401946.2
TNRC6B	ENST00000335727.13	c.116-3560T>C		intron_variant		1		ENSP00000338371.8
TNRC6B	ENST00000402203.5	c.224-3560T>C		intron_variant		1		ENSP00000384795.1
TNRC6B	ENST00000301923.13	c.224-3560T>C		intron_variant		5		ENSP00000306759.9

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48144 AN: 151416 Hom.: 8288 Cov.: 30

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.318 AC: 48176 AN: 151534 Hom.: 8301 Cov.: 30 AF XY: 0.326 AC XY: 24117 AN XY: 74002

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.314

Alfa AF: 0.337 Hom.: 10029

Bravo AF: 0.318

Asia WGS AF: 0.477 AC: 1656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.0
DANN	Benign	0.45

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: rs12628051; hg19: chr22-40654276;