rs3769956

Positions:

• chr2-161420790-G-A
• chr2-161420790-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TBR1	NM_006593.4	c.1190+533G>A		intron_variant		ENST00000389554.8	NP_006584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBR1	ENST00000389554.8	c.1190+533G>A		intron_variant		1	NM_006593.4	ENSP00000374205.3

Frequencies

GnomAD3 genomes AF: 0.0994 AC: 15103 AN: 152014 Hom.: 825 Cov.: 32

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: 20 AN: 310 Hom.: 0 Cov.: 0 AF XY: 0.0455 AC XY: 9 AN XY: 198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.0564

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.0994 AC: 15118 AN: 152132 Hom.: 828 Cov.: 32 AF XY: 0.0993 AC XY: 7379 AN XY: 74340

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.0666

Gnomad4 ASJ AF: 0.0545

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.0851

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.0802

Gnomad4 OTH AF: 0.0872

Alfa AF: 0.0735 Hom.: 469

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	19
DANN	Benign	0.80

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: rs3769956; hg19: chr2-162277301;