22-40195254-T-G

Variant names:

• chr22-40195254-T-G
• rs6001831
• NM_001162501.2:c.5+17114T>G

Variant summary

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

The NM_001162501.2(TNRC6B):​c.5+17114T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 152,114 control chromosomes in the GnomAD database, including 36,225 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 0.67 (36225 hom., cov: 32)
• Consequence: TNRC6B NM_001162501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.853

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC6B	NM_001162501.2	c.5+17114T>G		intron_variant	Intron 1 of 22	ENST00000454349.7	NP_001155973.1
TNRC6B	NM_015088.3	c.5+17114T>G		intron_variant	Intron 1 of 20		NP_055903.2
TNRC6B	NM_001024843.2	c.113+39072T>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.5+17114T>G		intron_variant	Intron 1 of 22	2	NM_001162501.2	ENSP00000401946.2

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102512 AN: 151996 Hom.: 36168 Cov.: 32

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.675 AC: 102626 AN: 152114 Hom.: 36225 Cov.: 32 AF XY: 0.672 AC XY: 49982 AN XY: 74334

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.597

Alfa AF: 0.647 Hom.: 4067

Bravo AF: 0.684

Asia WGS AF: 0.651 AC: 2265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.44

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: rs6001831; hg19: chr22-40591258;