Variant chr1-47994385-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001194986.2(TRABD2B):c.315C>T(p.His105=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,536,180 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 10 hom. )

Consequence

TRABD2B
NM_001194986.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.63

Variant links:

Genes affected

TRABD2B (HGNC:44200): (TraB domain containing 2B) Enables Wnt-protein binding activity and metalloendopeptidase activity. Involved in several processes, including negative regulation of Wnt signaling pathway; positive regulation of protein oxidation; and positive regulation of protein-containing complex assembly. Is integral component of organelle membrane and integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TRABD2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 1-47994385-G-A is Benign according to our data. Variant chr1-47994385-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2638809.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.63 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRABD2B	NM_001194986.2 linkuse as main transcript	c.315C>T	p.His105=	synonymous_variant	2/7	ENST00000606738.3	NP_001181915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRABD2B	ENST00000606738.3 linkuse as main transcript	c.315C>T	p.His105=	synonymous_variant	2/7	1	NM_001194986.2	ENSP00000476820	P1

Frequencies

GnomAD3 genomes

AF:

0.00211

AC:

321

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000506

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00998

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00260

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00143

AC:

193

AN:

134760

Hom.:

AF XY:

0.00140

AC XY:

103

AN XY:

73398

show subpopulations

Gnomad AFR exome

AF:

0.000776

Gnomad AMR exome

AF:

0.0000817

Gnomad ASJ exome

AF:

0.000241

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000178

Gnomad FIN exome

AF:

0.0123

Gnomad NFE exome

AF:

0.00209

Gnomad OTH exome

AF:

0.000724

GnomAD4 exome

AF:

0.00138

AC:

1908

AN:

1383826

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

1005

AN XY:

682848

show subpopulations

Gnomad4 AFR exome

AF:

0.000696

Gnomad4 AMR exome

AF:

0.0000840

Gnomad4 ASJ exome

AF:

0.000635

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0105

Gnomad4 NFE exome

AF:

0.00133

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.00211

AC:

321

AN:

152354

Hom.:

Cov.:

AF XY:

0.00256

AC XY:

191

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00998

Gnomad4 NFE

AF:

0.00260

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00377

Hom.:

Bravo

AF:

0.00108

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

TRABD2B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.13

DANN

Benign

0.68

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

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