rs4821940

chr22-40263569-T-Cchr22-40263569-T-G

Variant summary

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

The NM_001162501.2(TNRC6B):c.458-1119T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,088 control chromosomes in the GnomAD database, including 17,346 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 0.46 (17346 hom., cov: 32)
• Consequence: TNRC6B NM_001162501.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215

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]

LOC124905121 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNRC6B	NM_001162501.2	c.458-1119T>C		intron_variant		ENST00000454349.7
LOC124905121	XR_007068107.1	n.304-3201A>G		intron_variant, non_coding_transcript_variant
TNRC6B	NM_001024843.2	c.565+1396T>C		intron_variant
TNRC6B	NM_015088.3	c.458-1119T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNRC6B	ENST00000454349.7	c.458-1119T>C		intron_variant		2	NM_001162501.2	P3
TNRC6B	ENST00000335727.13	c.458-1119T>C		intron_variant		1
TNRC6B	ENST00000402203.5	c.565+1396T>C		intron_variant		1		A2
TNRC6B	ENST00000301923.13	c.565+1396T>C		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69322 AN: 151970 Hom.: 17332 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.456 AC: 69353 AN: 152088 Hom.: 17346 Cov.: 32 AF XY: 0.460 AC XY: 34168 AN XY: 74348

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.725

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.537

Gnomad4 OTH AF: 0.450

Alfa AF: 0.519 Hom.: 6674

Bravo AF: 0.447

Asia WGS AF: 0.594 AC: 2067 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	3.8
Dann	Benign	0.70

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: rs4821940; hg19: chr22-40659573;