2-161420470-T-C

Variant names:

• chr2-161420470-T-C
• rs10175058
• NM_006593.4:c.1190+213T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006593.4(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 NM_006593.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 10 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TBR1	NM_006593.4	c.1190+213T>C		intron_variant	Intron 5 of 5	ENST00000389554.8	NP_006584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBR1	ENST00000389554.8	c.1190+213T>C		intron_variant	Intron 5 of 5	1	NM_006593.4	ENSP00000374205.3

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

African (AFR) AF: 0.412 AC: 842 AN: 2046

American (AMR) AF: 0.512 AC: 781 AN: 1526

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1219 AN: 2228

East Asian (EAS) AF: 0.527 AC: 2648 AN: 5026

South Asian (SAS) AF: 0.418 AC: 1605 AN: 3840

European-Finnish (FIN) AF: 0.228 AC: 1360 AN: 5968

Middle Eastern (MID) AF: 0.489 AC: 180 AN: 368

European-Non Finnish (NFE) AF: 0.332 AC: 17489 AN: 52624

Other (OTH) AF: 0.370 AC: 1739 AN: 4698

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

African (AFR) AF: 0.557 AC: 20891 AN: 37498

American (AMR) AF: 0.624 AC: 8603 AN: 13796

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2262 AN: 3410

East Asian (EAS) AF: 0.570 AC: 2691 AN: 4722

South Asian (SAS) AF: 0.601 AC: 2551 AN: 4246

European-Finnish (FIN) AF: 0.404 AC: 3360 AN: 8322

Middle Eastern (MID) AF: 0.658 AC: 183 AN: 278

European-Non Finnish (NFE) AF: 0.495 AC: 32654 AN: 66014

Other (OTH) AF: 0.550 AC: 1047 AN: 1902

Alfa AF: 0.523 Hom.: 55815

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
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10175058; hg19: chr2-162276981;