chr22-40217032-A-G

Variant names:

• chr22-40217032-A-G
• rs138022
• NM_001162501.2:c.6-28983A>G

Variant summary

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

The NM_001162501.2(TNRC6B):​c.6-28983A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 151,978 control chromosomes in the GnomAD database, including 33,582 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 0.62 (33582 hom., cov: 30)
• Consequence: TNRC6B NM_001162501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC6B	NM_001162501.2	c.6-28983A>G		intron_variant	Intron 1 of 22	ENST00000454349.7	NP_001155973.1
TNRC6B	NM_015088.3	c.6-28983A>G		intron_variant	Intron 1 of 20		NP_055903.2
TNRC6B	NM_001024843.2	c.114-28983A>G		intron_variant	Intron 4 of 23		NP_001020014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000454349.7	c.6-28983A>G		intron_variant	Intron 1 of 22	2	NM_001162501.2	ENSP00000401946.2

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94110 AN: 151860 Hom.: 33575 Cov.: 30

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.619 AC: 94142 AN: 151978 Hom.: 33582 Cov.: 30 AF XY: 0.630 AC XY: 46768 AN XY: 74278

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.720

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.780

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.694

Alfa AF: 0.676 Hom.: 5943

Bravo AF: 0.607

Asia WGS AF: 0.809 AC: 2814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.23
DANN	Benign	0.43

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: rs138022; hg19: chr22-40613036;