Variant 3-138161901-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016216.4(DBR1):c.1623C>T(p.Asp541=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,591,570 control chromosomes in the GnomAD database, including 342,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 30213 hom., cov: 33)

Exomes 𝑓: 0.66 ( 312430 hom. )

Consequence

DBR1
NM_016216.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.07

Variant links:

Genes affected

DBR1 (HGNC:15594): (debranching RNA lariats 1) The protein encoded by this gene is an RNA lariat debranching enzyme that hydrolyzes 2'-5' prime branched phosphodiester bonds. The encoded protein specifically targets the bonds at the branch point of excised lariat intron RNA, converting them to linear molecules that are then degraded. This protein may also be involved in retroviral replication. [provided by RefSeq, Nov 2011]

DBR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 3-138161901-G-A is Benign according to our data. Variant chr3-138161901-G-A is described in ClinVar as [Benign]. Clinvar id is 2115209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DBR1	NM_016216.4 linkuse as main transcript	c.1623C>T	p.Asp541=	synonymous_variant	8/8	ENST00000260803.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DBR1	ENST00000260803.9 linkuse as main transcript	c.1623C>T	p.Asp541=	synonymous_variant	8/8	1	NM_016216.4	P1	Q9UK59-1

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

94764

AN:

151842

Hom.:

30206

Cov.:

show subpopulations

Gnomad AFR

AF:

0.491

Gnomad AMI

AF:

0.479

Gnomad AMR

AF:

0.682

Gnomad ASJ

AF:

0.701

Gnomad EAS

AF:

0.585

Gnomad SAS

AF:

0.607

Gnomad FIN

AF:

0.667

Gnomad MID

AF:

0.694

Gnomad NFE

AF:

0.687

Gnomad OTH

AF:

0.649

GnomAD3 exomes

AF:

0.628

AC:

153823

AN:

244874

Hom.:

47414

AF XY:

0.631

AC XY:

83460

AN XY:

132202

show subpopulations

Gnomad AFR exome

AF:

0.477

Gnomad AMR exome

AF:

0.606

Gnomad ASJ exome

AF:

0.673

Gnomad EAS exome

AF:

0.573

Gnomad SAS exome

AF:

0.581

Gnomad FIN exome

AF:

0.653

Gnomad NFE exome

AF:

0.669

Gnomad OTH exome

AF:

0.641

GnomAD4 exome

AF:

0.664

AC:

955649

AN:

1439610

Hom.:

312430

Cov.:

AF XY:

0.662

AC XY:

474230

AN XY:

716210

show subpopulations

Gnomad4 AFR exome

AF:

0.477

Gnomad4 AMR exome

AF:

0.620

Gnomad4 ASJ exome

AF:

0.676

Gnomad4 EAS exome

AF:

0.548

Gnomad4 SAS exome

AF:

0.591

Gnomad4 FIN exome

AF:

0.657

Gnomad4 NFE exome

AF:

0.682

Gnomad4 OTH exome

AF:

0.651

GnomAD4 genome

AF:

0.624

AC:

94808

AN:

151960

Hom.:

30213

Cov.:

AF XY:

0.624

AC XY:

46362

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.491

Gnomad4 AMR

AF:

0.683

Gnomad4 ASJ

AF:

0.701

Gnomad4 EAS

AF:

0.584

Gnomad4 SAS

AF:

0.608

Gnomad4 FIN

AF:

0.667

Gnomad4 NFE

AF:

0.687

Gnomad4 OTH

AF:

0.644

Alfa

AF:

0.670

Hom.:

42589

Bravo

AF:

0.620

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 89% of patients studied by a panel of primary immunodeficiencies. Number of patients: 85. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.8

DANN

Benign

0.23

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