chr22-40301577-C-T

Position:

• chr22-40301577-C-T

Variant summary

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

The NM_001162501.2(TNRC6B):​c.4120+244C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 503,550 control chromosomes in the GnomAD database, including 118,721 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 0.73 (41847 hom., cov: 31)
  • Exomes 𝑓: 0.66 (76874 hom.)
• Consequence: TNRC6B NM_001162501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNRC6B	NM_001162501.2	c.4120+244C>T		intron_variant		ENST00000454349.7	NP_001155973.1
TNRC6B	NM_001024843.2	c.1708+244C>T		intron_variant			NP_001020014.1
TNRC6B	NM_015088.3	c.3790+244C>T		intron_variant			NP_055903.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000454349.7	c.4120+244C>T		intron_variant		2	NM_001162501.2	ENSP00000401946	P3

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110702 AN: 151714 Hom.: 41778 Cov.: 31

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.668

GnomAD4 exome AF: 0.658 AC: 231487 AN: 351720 Hom.: 76874 AF XY: 0.664 AC XY: 121577 AN XY: 183070

Gnomad4 AFR exome AF: 0.920

Gnomad4 AMR exome AF: 0.694

Gnomad4 ASJ exome AF: 0.618

Gnomad4 EAS exome AF: 0.451

Gnomad4 SAS exome AF: 0.800

Gnomad4 FIN exome AF: 0.610

Gnomad4 NFE exome AF: 0.656

Gnomad4 OTH exome AF: 0.653

GnomAD4 genome AF: 0.730 AC: 110831 AN: 151830 Hom.: 41847 Cov.: 31 AF XY: 0.725 AC XY: 53834 AN XY: 74208

Gnomad4 AFR AF: 0.927

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.801

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.667

Alfa AF: 0.668 Hom.: 76031

Bravo AF: 0.740

Asia WGS AF: 0.680 AC: 2364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.80
DANN	Benign	0.18

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: rs139909; hg19: chr22-40697581;