Genetic Variant ENST00000495973.5:n.408G>T (chr7-45107057-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000495973.5(TBRG4):n.408G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 151,828 control chromosomes in the GnomAD database, including 37,379 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 0.70 ( 37369 hom., cov: 30)

Exomes 𝑓: 0.83 ( 10 hom. )

Consequence

TBRG4
ENST00000495973.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.07

Publications

11 publications found

Variant links:

Genes affected

TBRG4 (HGNC:17443): (transforming growth factor beta regulator 4) Enables RNA binding activity. Involved in mitochondrial mRNA processing and regulation of mitochondrial mRNA stability. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

TBRG4 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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TBRG4	NM_004749.4 link	c.412-1293G>T	intron_variant	Intron 2 of 10	ENST00000258770.8	NP_004740.2	Q969Z0-1
TBRG4	NM_001261834.2 link	c.445-1293G>T	intron_variant	Intron 2 of 10		NP_001248763.1	B3KRS4B4DU42
TBRG4	NM_030900.4 link	c.412-1293G>T	intron_variant	Intron 2 of 8		NP_112162.1	Q969Z0-2
TBRG4	NM_199122.3 link	c.412-1293G>T	intron_variant	Intron 2 of 8		NP_954573.1	Q969Z0-2B3KM73

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBRG4	ENST00000258770.8 link	c.412-1293G>T		intron_variant	Intron 2 of 10	1	NM_004749.4	ENSP00000258770.3		Q969Z0-1

Frequencies

GnomAD3 genomes

AF:

0.699

AC:

105989

AN:

151682

Hom.:

37340

Cov.:

show subpopulations

Gnomad AFR

AF:

0.701

Gnomad AMI

AF:

0.667

Gnomad AMR

AF:

0.689

Gnomad ASJ

AF:

0.726

Gnomad EAS

AF:

0.394

Gnomad SAS

AF:

0.685

Gnomad FIN

AF:

0.737

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.717

Gnomad OTH

AF:

0.696

GnomAD4 exome

AF:

0.833

AC:

AN:

Hom.:

Cov.:

AF XY:

0.818

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.750

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.699

AC:

106050

AN:

151798

Hom.:

37369

Cov.:

AF XY:

0.695

AC XY:

51593

AN XY:

74190

show subpopulations

African (AFR)

AF:

0.701

AC:

28976

AN:

41338

American (AMR)

AF:

0.688

AC:

10521

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.726

AC:

2520

AN:

3470

East Asian (EAS)

AF:

0.394

AC:

2019

AN:

5130

South Asian (SAS)

AF:

0.684

AC:

3298

AN:

4820

European-Finnish (FIN)

AF:

0.737

AC:

7770

AN:

10536

Middle Eastern (MID)

AF:

0.639

AC:

188

AN:

294

European-Non Finnish (NFE)

AF:

0.717

AC:

48700

AN:

67916

Other (OTH)

AF:

0.690

AC:

1454

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1594

3188

4781

6375

7969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

818

1636

2454

3272

4090

<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:

0.712

Hom.:

76826

Bravo

AF:

0.692

Asia WGS

AF:

0.579

AC:

2019

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.38

(source)

DANN

Benign

0.54

PhyloP100

-1.1

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

Computational scores

Splicing

Publications

Other links and lift over