Variant chr9-129807253-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The ENST00000259339.7(TOR1B):c.531C>T(p.Asp177Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 1,614,090 control chromosomes in the GnomAD database, including 286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 24 hom., cov: 32)

Exomes 𝑓: 0.017 ( 262 hom. )

Consequence

TOR1B
ENST00000259339.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.71

Variant links:

Genes affected

TOR1B (HGNC:11995): (torsin family 1 member B) The protein encoded by this gene is an ATPase found primarily in the endoplasmic reticulum and nuclear envelope. This gene has a highly-similar neighboring gene, TOR1A, that encodes a protein that is likely to interact in a complex with this protein. Finally, this protein may act as a chaperone and play a role in maintaining the integrity of the nuclear envelope and endoplasmic reticulum. Several transcript variants, some protein-coding and others non-protein coding, have been found for this gene. [provided by RefSeq, Dec 2015]

TOR1B links:

TOR1B (HGNC:):

TOR1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 9-129807253-C-T is Benign according to our data. Variant chr9-129807253-C-T is described in ClinVar as [Benign]. Clinvar id is 770585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.71 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0117 (1780/152222) while in subpopulation AMR AF= 0.0239 (365/15286). AF 95% confidence interval is 0.0219. There are 24 homozygotes in gnomad4. There are 790 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1780 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOR1B	NM_014506.3 linkuse as main transcript	c.531C>T	p.Asp177Asp	synonymous_variant	3/5	ENST00000259339.7	NP_055321.1	O14657

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TOR1B	ENST00000259339.7 linkuse as main transcript	c.531C>T	p.Asp177Asp	synonymous_variant	3/5	1	NM_014506.3	ENSP00000259339.2	O14657
TOR1B	ENST00000427860.1 linkuse as main transcript	c.408+2915C>T		intron_variant		3		ENSP00000411912.1	H0Y7C8
TOR1B	ENST00000488169.1 linkuse as main transcript	n.188C>T		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1779

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00340

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0239

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0178

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.0101

AC:

2544

AN:

251490

Hom.:

AF XY:

0.0102

AC XY:

1390

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00271

Gnomad AMR exome

AF:

0.0123

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.00300

Gnomad NFE exome

AF:

0.0168

Gnomad OTH exome

AF:

0.00928

GnomAD4 exome

AF:

0.0170

AC:

24836

AN:

1461868

Hom.:

262

Cov.:

AF XY:

0.0165

AC XY:

11968

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00266

Gnomad4 AMR exome

AF:

0.0129

Gnomad4 ASJ exome

AF:

0.00337

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000487

Gnomad4 FIN exome

AF:

0.00358

Gnomad4 NFE exome

AF:

0.0205

Gnomad4 OTH exome

AF:

0.0162

GnomAD4 genome

AF:

0.0117

AC:

1780

AN:

152222

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

790

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00339

Gnomad4 AMR

AF:

0.0239

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.0178

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0149

Hom.:

Bravo

AF:

0.0132

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0189

EpiControl

AF:

0.0200

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

7.8

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over