Genetic Variant TNRC18:c.6746-145G>A (chr7-5316217-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001080495.3(TNRC18):c.6746-145G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 537,080 control chromosomes in the GnomAD database, including 194,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.85 ( 53606 hom., cov: 24)

Exomes 𝑓: 0.85 ( 140868 hom. )

Consequence

TNRC18
NM_001080495.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.833

Publications

2 publications found

Variant links:

Genes affected

TNRC18 (HGNC:11962): (trinucleotide repeat containing 18) Predicted to enable chromatin binding activity. Located in cytosol; mitochondrion; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TNRC18 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 7-5316217-C-T is Benign according to our data. Variant chr7-5316217-C-T is described in ClinVar as Benign. ClinVar VariationId is 1291078.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC18	NM_001080495.3 link	c.6746-145G>A		intron_variant	Intron 24 of 29	ENST00000430969.6	NP_001073964.2	O15417-1A3KMH2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNRC18	ENST00000430969.6 link	c.6746-145G>A	intron_variant	Intron 24 of 29	5	NM_001080495.3	ENSP00000395538.1	O15417-1
TNRC18	ENST00000399537.8 link	c.6746-145G>A	intron_variant	Intron 24 of 29	5		ENSP00000382452.4	H9KVB4
TNRC18	ENST00000328270.3 link	c.185-145G>A	intron_variant	Intron 2 of 4	5		ENSP00000329902.3	H7BXS9

Frequencies

GnomAD3 genomes

AF:

0.845

AC:

126548

AN:

149756

Hom.:

53563

Cov.:

show subpopulations

Gnomad AFR

AF:

0.816

Gnomad AMI

AF:

0.836

Gnomad AMR

AF:

0.862

Gnomad ASJ

AF:

0.824

Gnomad EAS

AF:

0.968

Gnomad SAS

AF:

0.830

Gnomad FIN

AF:

0.891

Gnomad MID

AF:

0.824

Gnomad NFE

AF:

0.845

Gnomad OTH

AF:

0.851

GnomAD4 exome

AF:

0.853

AC:

330205

AN:

387210

Hom.:

140868

AF XY:

0.850

AC XY:

174954

AN XY:

205738

show subpopulations

African (AFR)

AF:

0.821

AC:

6608

AN:

8044

American (AMR)

AF:

0.869

AC:

7735

AN:

8906

Ashkenazi Jewish (ASJ)

AF:

0.841

AC:

10761

AN:

12800

East Asian (EAS)

AF:

0.965

AC:

22217

AN:

23016

South Asian (SAS)

AF:

0.825

AC:

28104

AN:

34056

European-Finnish (FIN)

AF:

0.878

AC:

26424

AN:

30096

Middle Eastern (MID)

AF:

0.846

AC:

1556

AN:

1840

European-Non Finnish (NFE)

AF:

0.845

AC:

207429

AN:

245618

Other (OTH)

AF:

0.848

AC:

19371

AN:

22834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

2200

4400

6599

8799

10999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

758

1516

2274

3032

3790

<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:

0.845

AC:

126644

AN:

149870

Hom.:

53606

Cov.:

AF XY:

0.848

AC XY:

61864

AN XY:

72974

show subpopulations

African (AFR)

AF:

0.816

AC:

33098

AN:

40538

American (AMR)

AF:

0.862

AC:

12890

AN:

14952

Ashkenazi Jewish (ASJ)

AF:

0.824

AC:

2857

AN:

3468

East Asian (EAS)

AF:

0.968

AC:

4859

AN:

5022

South Asian (SAS)

AF:

0.829

AC:

3946

AN:

4760

European-Finnish (FIN)

AF:

0.891

AC:

8952

AN:

10050

Middle Eastern (MID)

AF:

0.821

AC:

238

AN:

290

European-Non Finnish (NFE)

AF:

0.845

AC:

57270

AN:

67800

Other (OTH)

AF:

0.853

AC:

1777

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

924

1848

2771

3695

4619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

880

1760

2640

3520

4400

<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:

0.853

Hom.:

11201

Bravo

AF:

0.845

Asia WGS

AF:

0.891

AC:

3097

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 15, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.56

(source)

DANN

Benign

0.63

PhyloP100

-0.83

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over