dbSNP rs3769956: TBR1:c.1190+533G>A (chr2-161420790-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_006593.4(TBR1):c.1190+533G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0993 in 152,442 control chromosomes in the GnomAD database, including 828 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 0.099 ( 828 hom., cov: 32)

Exomes 𝑓: 0.065 ( 0 hom. )

Consequence

TBR1
NM_006593.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.15

Publications

2 publications found

Variant links:

Genes affected

TBR1 (HGNC:11590): (T-box brain transcription factor 1) This gene is a member of a conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of numerous developmental processes. In mouse, the ortholog of this gene is expressed in the cerebral cortex, hippocampus, amygdala and olfactory bulb and is thought to play an important role in neuronal migration and axonal projection. In mouse, the C-terminal region of this protein was found to be necessary and sufficient for association with the guanylate kinase domain of calcium/calmodulin-dependent serine protein kinase. [provided by RefSeq, Dec 2015]

TBR1 Gene-Disease associations (from GenCC):

autism
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
occipital pachygyria and polymicrogyria
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TBR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBR1	NM_006593.4 link	c.1190+533G>A		intron_variant	Intron 5 of 5	ENST00000389554.8	NP_006584.1	Q16650-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBR1	ENST00000389554.8 link	c.1190+533G>A		intron_variant	Intron 5 of 5	1	NM_006593.4	ENSP00000374205.3		Q16650-1

Frequencies

GnomAD3 genomes

AF:

0.0994

AC:

15103

AN:

152014

Hom.:

825

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.0664

Gnomad ASJ

AF:

0.0545

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.0852

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0802

Gnomad OTH

AF:

0.0848

GnomAD4 exome

AF:

0.0645

AC:

AN:

310

Hom.:

Cov.:

AF XY:

0.0455

AC XY:

AN XY:

198

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.100

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.100

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0564

AC:

AN:

266

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0994

AC:

15118

AN:

152132

Hom.:

828

Cov.:

AF XY:

0.0993

AC XY:

7379

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.141

AC:

5861

AN:

41494

American (AMR)

AF:

0.0666

AC:

1019

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0545

AC:

189

AN:

3468

East Asian (EAS)

AF:

0.104

AC:

536

AN:

5174

South Asian (SAS)

AF:

0.0851

AC:

410

AN:

4820

European-Finnish (FIN)

AF:

0.127

AC:

1346

AN:

10566

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0802

AC:

5454

AN:

67998

Other (OTH)

AF:

0.0872

AC:

184

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

698

1396

2093

2791

3489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<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:

0.0790

Hom.:

788

Bravo

AF:

0.0959

Asia WGS

AF:

0.105

AC:

363

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

3.2

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