3-138161901-G-A

Variant names:

• chr3-138161901-G-A
• rs2622736
• NM_016216.4:c.1623C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_016216.4(DBR1):​c.1623C>T​(p.Asp541Asp) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.07
• Publications: 19 publications found

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 Gene-Disease associations (from GenCC):

• encephalitis, acute, infection (viral)-induced, susceptibility to, 11

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• xerosis and growth failure with immune and pulmonary dysfunction syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016216.4. 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
	DBR1	NM_016216.4	MANE Select	c.1623C>T	p.Asp541Asp	synonymous	Exon 8 of 8	NP_057300.2	Q9UK59-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBR1	ENST00000260803.9	TSL:1 MANE Select	c.1623C>T	p.Asp541Asp	synonymous	Exon 8 of 8	ENSP00000260803.4	Q9UK59-1
	DBR1	ENST00000698924.1		c.1542C>T	p.Asp514Asp	synonymous	Exon 7 of 7	ENSP00000514035.1	A0A8V8TNX0
	DBR1	ENST00000698922.1		c.1398C>T	p.Asp466Asp	synonymous	Exon 7 of 7	ENSP00000514033.1	A0A8V8TMF7

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94764 AN: 151842 Hom.: 30206 Cov.: 33

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

GnomAD2 exomes AF: 0.628 AC: 153823 AN: 244874 AF XY: 0.631

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 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.: 31 AF XY: 0.662 AC XY: 474230 AN XY: 716210

African (AFR) AF: 0.477 AC: 15823 AN: 33164

American (AMR) AF: 0.620 AC: 27425 AN: 44210

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 17406 AN: 25746

East Asian (EAS) AF: 0.548 AC: 21601 AN: 39402

South Asian (SAS) AF: 0.591 AC: 50239 AN: 85056

European-Finnish (FIN) AF: 0.657 AC: 34781 AN: 52960

Middle Eastern (MID) AF: 0.641 AC: 3668 AN: 5724

European-Non Finnish (NFE) AF: 0.682 AC: 745997 AN: 1093842

Other (OTH) AF: 0.651 AC: 38709 AN: 59506

GnomAD4 genome AF: 0.624 AC: 94808 AN: 151960 Hom.: 30213 Cov.: 33 AF XY: 0.624 AC XY: 46362 AN XY: 74294

African (AFR) AF: 0.491 AC: 20330 AN: 41432

American (AMR) AF: 0.683 AC: 10430 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2433 AN: 3470

East Asian (EAS) AF: 0.584 AC: 3019 AN: 5168

South Asian (SAS) AF: 0.608 AC: 2934 AN: 4826

European-Finnish (FIN) AF: 0.667 AC: 7033 AN: 10546

Middle Eastern (MID) AF: 0.685 AC: 200 AN: 292

European-Non Finnish (NFE) AF: 0.687 AC: 46635 AN: 67928

Other (OTH) AF: 0.644 AC: 1358 AN: 2110

Alfa AF: 0.666 Hom.: 52474

Bravo AF: 0.620

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.23
PhyloP100		-2.1
Mutation Taster		=20/80	disease causing

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

Other links and lift over

dbSNP: rs2622736; hg19: chr3-137880743; COSMIC: COSV108077177; COSMIC: COSV108077177;