Variant 11-49032278-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_001206626.2(TRIM49B):c.414G>A(p.Glu138=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00666 in 1,612,798 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 9 hom., cov: 31)

Exomes 𝑓: 0.0068 ( 91 hom. )

Consequence

TRIM49B
NM_001206626.2 splice_region, synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.104

Variant links:

Genes affected

TRIM49B (HGNC:42955): (tripartite motif containing 49B)

TRIM49B 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=-0.93).

BP6

Variant 11-49032278-G-A is Benign according to our data. Variant chr11-49032278-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2641777.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.104 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM49B	NM_001206626.2 linkuse as main transcript	c.414G>A	p.Glu138=	splice_region_variant, synonymous_variant	3/7	ENST00000332682.9	NP_001193555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM49B	ENST00000332682.9 linkuse as main transcript	c.414G>A	p.Glu138=	splice_region_variant, synonymous_variant	3/7	1	NM_001206626.2	ENSP00000330216	P1
TRIM49B	ENST00000622138.4 linkuse as main transcript	c.414G>A	p.Glu138=	splice_region_variant, synonymous_variant	4/8	1		ENSP00000481457	P1

Frequencies

GnomAD3 genomes

AF:

0.00553

AC:

841

AN:

151998

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00708

Gnomad ASJ

AF:

0.0545

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00685

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.00701

AC:

1716

AN:

244864

Hom.:

AF XY:

0.00720

AC XY:

961

AN XY:

133390

show subpopulations

Gnomad AFR exome

AF:

0.00199

Gnomad AMR exome

AF:

0.00499

Gnomad ASJ exome

AF:

0.0552

Gnomad EAS exome

AF:

0.0000549

Gnomad SAS exome

AF:

0.00246

Gnomad FIN exome

AF:

0.000603

Gnomad NFE exome

AF:

0.00755

Gnomad OTH exome

AF:

0.00824

GnomAD4 exome

AF:

0.00678

AC:

9904

AN:

1460682

Hom.:

Cov.:

AF XY:

0.00692

AC XY:

5032

AN XY:

726664

show subpopulations

Gnomad4 AFR exome

AF:

0.00132

Gnomad4 AMR exome

AF:

0.00497

Gnomad4 ASJ exome

AF:

0.0602

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00272

Gnomad4 FIN exome

AF:

0.000674

Gnomad4 NFE exome

AF:

0.00650

Gnomad4 OTH exome

AF:

0.00886

GnomAD4 genome

AF:

0.00553

AC:

841

AN:

152116

Hom.:

Cov.:

AF XY:

0.00557

AC XY:

414

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.00707

Gnomad4 ASJ

AF:

0.0545

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00685

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.0115

Hom.:

Bravo

AF:

0.00628

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

Feb 01, 2023

TRIM49B: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.9

DANN

Benign

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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