chr22-40316633-G-A

Position:

• chr22-40316633-G-A

Variant summary

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

The NM_001162501.2(TNRC6B):​c.4974+621G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,976 control chromosomes in the GnomAD database, including 7,622 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 0.30 (7622 hom., cov: 31)
• Consequence: TNRC6B NM_001162501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNRC6B	NM_001162501.2	c.4974+621G>A		intron_variant		ENST00000454349.7	NP_001155973.1
TNRC6B	NM_015088.3	c.4644+621G>A		intron_variant			NP_055903.2
TNRC6B	NM_001024843.2	c.2562+621G>A		intron_variant			NP_001020014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000454349.7	c.4974+621G>A		intron_variant		2	NM_001162501.2	ENSP00000401946.2

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44907 AN: 151858 Hom.: 7607 Cov.: 31

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.296 AC: 44953 AN: 151976 Hom.: 7622 Cov.: 31 AF XY: 0.304 AC XY: 22571 AN XY: 74276

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.293

Alfa AF: 0.334 Hom.: 4249

Bravo AF: 0.294

Asia WGS AF: 0.476 AC: 1655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.88
DANN	Benign	0.31

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: rs6001877; hg19: chr22-40712637;