dbSNP rs200710085: TRIM49B:p.Glu138Glu (chr11-49032278-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001206626.2(TRIM49B):c.414G>A(p.Glu138Glu) 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

Publications

0 publications found

Variant links:

Genes affected

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

TRIM49B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206626.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM49B	NM_001206626.2	MANE Select	c.414G>A	p.Glu138Glu	splice_region synonymous	Exon 3 of 7	NP_001193555.1	A6NDI0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM49B	ENST00000332682.9	TSL:1 MANE Select	c.414G>A	p.Glu138Glu	splice_region synonymous	Exon 3 of 7	ENSP00000330216.7	A6NDI0
	TRIM49B	ENST00000622138.4	TSL:1	c.414G>A	p.Glu138Glu	splice_region synonymous	Exon 4 of 8	ENSP00000481457.1	A6NDI0

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

GnomAD2 exomes

AF:

0.00701

AC:

1716

AN:

244864

AF XY:

0.00720

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 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

African (AFR)

AF:

0.00132

AC:

AN:

33440

American (AMR)

AF:

0.00497

AC:

222

AN:

44642

Ashkenazi Jewish (ASJ)

AF:

0.0602

AC:

1572

AN:

26116

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00272

AC:

234

AN:

86150

European-Finnish (FIN)

AF:

0.000674

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00730

AC:

AN:

5202

European-Non Finnish (NFE)

AF:

0.00650

AC:

7223

AN:

1111762

Other (OTH)

AF:

0.00886

AC:

534

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

538

1077

1615

2154

2692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

272

544

816

1088

1360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00553

AC:

841

AN:

152116

Hom.:

Cov.:

AF XY:

0.00557

AC XY:

414

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

41496

American (AMR)

AF:

0.00707

AC:

108

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0545

AC:

189

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00228

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00685

AC:

466

AN:

67988

Other (OTH)

AF:

0.00427

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

124

166

207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0115

Hom.:

Bravo

AF:

0.00628

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.9

(source)

DANN

Benign

0.24

PhyloP100

0.10

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over