chr22-40307884-C-G

Position:

• chr22-40307884-C-G

Variant summary

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

The NM_001162501.2(TNRC6B):​c.4121-628C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,888 control chromosomes in the GnomAD database, including 8,570 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 0.31 (8570 hom., cov: 31)
• Consequence: TNRC6B NM_001162501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNRC6B	NM_001162501.2	c.4121-628C>G		intron_variant		ENST00000454349.7	NP_001155973.1
TNRC6B	NM_015088.3	c.3791-628C>G		intron_variant			NP_055903.2
TNRC6B	NM_001024843.2	c.1709-628C>G		intron_variant			NP_001020014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000454349.7	c.4121-628C>G		intron_variant		2	NM_001162501.2	ENSP00000401946.2

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46335 AN: 151770 Hom.: 8566 Cov.: 31

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.305 AC: 46368 AN: 151888 Hom.: 8570 Cov.: 31 AF XY: 0.296 AC XY: 22001 AN XY: 74244

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.0130

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.255

Alfa AF: 0.118 Hom.: 142

Bravo AF: 0.308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.28

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: rs139910; hg19: chr22-40703888;