2-161420470-T-C

Position:

• chr2-161420470-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000389554.8(TBR1):​c.1190+213T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.53 (20305 hom., cov: 19)
  • Exomes 𝑓: 0.36 (7965 hom.)
• Consequence: TBR1 ENST00000389554.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBR1	NM_006593.4	c.1190+213T>C		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+213T>C		intron_variant		1	NM_006593.4	ENSP00000374205	P1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 74702 AN: 140996 Hom.: 20293 Cov.: 19

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.555

GnomAD4 exome AF: 0.356 AC: 27863 AN: 78324 Hom.: 7965 Cov.: 3 AF XY: 0.358 AC XY: 15002 AN XY: 41864

Gnomad4 AFR exome AF: 0.412

Gnomad4 AMR exome AF: 0.512

Gnomad4 ASJ exome AF: 0.547

Gnomad4 EAS exome AF: 0.527

Gnomad4 SAS exome AF: 0.418

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.332

Gnomad4 OTH exome AF: 0.370

GnomAD4 genome AF: 0.530 AC: 74738 AN: 141084 Hom.: 20305 Cov.: 19 AF XY: 0.530 AC XY: 35995 AN XY: 67918

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.550

Alfa AF: 0.517 Hom.: 36691

Bravo AF: 0.555

Asia WGS AF: 0.528 AC: 1836 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.74

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: rs10175058; hg19: chr2-162276981;