dbSNP rs139909: TNRC6B:c.4120+244C>T (chr22-40301577-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.472

Publications

24 publications found

Variant links:

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]

TNRC6B Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
global developmental delay with speech and behavioral abnormalities
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TNRC6B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
TNRC6B	NM_001162501.2 link	c.4120+244C>T	intron_variant	Intron 15 of 22	ENST00000454349.7	NP_001155973.1	Q9UPQ9-3
TNRC6B	NM_015088.3 link	c.3790+244C>T	intron_variant	Intron 13 of 20		NP_055903.2	Q9UPQ9-1
TNRC6B	NM_001024843.2 link	c.1708+244C>T	intron_variant	Intron 16 of 23		NP_001020014.1	Q9UPQ9-2A0A024R1N5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000454349.7 link	c.4120+244C>T		intron_variant	Intron 15 of 22	2	NM_001162501.2	ENSP00000401946.2		Q9UPQ9-3

Frequencies

GnomAD3 genomes

AF:

0.730

AC:

110702

AN:

151714

Hom.:

41778

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.920

AC:

9305

AN:

10112

American (AMR)

AF:

0.694

AC:

8635

AN:

12440

Ashkenazi Jewish (ASJ)

AF:

0.618

AC:

7079

AN:

11456

East Asian (EAS)

AF:

0.451

AC:

11282

AN:

25034

South Asian (SAS)

AF:

0.800

AC:

24423

AN:

30538

European-Finnish (FIN)

AF:

0.610

AC:

13812

AN:

22630

Middle Eastern (MID)

AF:

0.613

AC:

1016

AN:

1658

European-Non Finnish (NFE)

AF:

0.656

AC:

142137

AN:

216724

Other (OTH)

AF:

0.653

AC:

13798

AN:

21128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

3490

6980

10470

13960

17450

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

670

1340

2010

2680

3350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.730

AC:

110831

AN:

151830

Hom.:

41847

Cov.:

AF XY:

0.725

AC XY:

53834

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.927

AC:

38436

AN:

41480

American (AMR)

AF:

0.672

AC:

10230

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.627

AC:

2173

AN:

3464

East Asian (EAS)

AF:

0.432

AC:

2221

AN:

5138

South Asian (SAS)

AF:

0.801

AC:

3859

AN:

4818

European-Finnish (FIN)

AF:

0.614

AC:

6471

AN:

10532

Middle Eastern (MID)

AF:

0.592

AC:

173

AN:

292

European-Non Finnish (NFE)

AF:

0.666

AC:

45237

AN:

67874

Other (OTH)

AF:

0.667

AC:

1401

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1402

2803

4205

5606

7008

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

824

1648

2472

3296

4120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.682

Hom.:

158101

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

(source)

DANN

Benign

0.18

PhyloP100

-0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over