3-138161853-A-G

Variant names:

• chr3-138161853-A-G
• rs9851548
• NM_016216.4:c.*36T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016216.4(DBR1):​c.*36T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 1,552,550 control chromosomes in the GnomAD database, including 354,892 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (30256 hom., cov: 33)
  • Exomes 𝑓: 0.68 (324636 hom.)
• Consequence: DBR1 NM_016216.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0250
• Publications: 9 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 3-138161853-A-G is Benign according to our data. Variant chr3-138161853-A-G is described in ClinVar as Benign. ClinVar VariationId is 2687947.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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.*36T>C		3_prime_UTR	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.*36T>C		3_prime_UTR	Exon 8 of 8	ENSP00000260803.4	Q9UK59-1
	DBR1	ENST00000698924.1		c.*36T>C		3_prime_UTR	Exon 7 of 7	ENSP00000514035.1	A0A8V8TNX0
	DBR1	ENST00000698922.1		c.*36T>C		3_prime_UTR	Exon 7 of 7	ENSP00000514033.1	A0A8V8TMF7

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94848 AN: 151962 Hom.: 30247 Cov.: 33

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.649

GnomAD2 exomes AF: 0.648 AC: 156163 AN: 241066 AF XY: 0.652

Gnomad AFR exome AF: 0.485

Gnomad AMR exome AF: 0.625

Gnomad ASJ exome AF: 0.701

Gnomad EAS exome AF: 0.593

Gnomad FIN exome AF: 0.668

Gnomad NFE exome AF: 0.690

Gnomad OTH exome AF: 0.667

GnomAD4 exome AF: 0.679 AC: 950412 AN: 1400470 Hom.: 324636 Cov.: 23 AF XY: 0.677 AC XY: 472681 AN XY: 697796

African (AFR) AF: 0.485 AC: 15662 AN: 32270

American (AMR) AF: 0.636 AC: 27758 AN: 43636

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 17175 AN: 24710

East Asian (EAS) AF: 0.561 AC: 22061 AN: 39344

South Asian (SAS) AF: 0.608 AC: 50365 AN: 82812

European-Finnish (FIN) AF: 0.669 AC: 35305 AN: 52768

Middle Eastern (MID) AF: 0.651 AC: 3652 AN: 5606

European-Non Finnish (NFE) AF: 0.697 AC: 739706 AN: 1061130

Other (OTH) AF: 0.665 AC: 38728 AN: 58194

GnomAD4 genome AF: 0.624 AC: 94894 AN: 152080 Hom.: 30256 Cov.: 33 AF XY: 0.624 AC XY: 46416 AN XY: 74360

African (AFR) AF: 0.490 AC: 20327 AN: 41456

American (AMR) AF: 0.683 AC: 10449 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2435 AN: 3472

East Asian (EAS) AF: 0.584 AC: 3014 AN: 5162

South Asian (SAS) AF: 0.608 AC: 2930 AN: 4820

European-Finnish (FIN) AF: 0.668 AC: 7063 AN: 10574

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

European-Non Finnish (NFE) AF: 0.687 AC: 46679 AN: 67980

Other (OTH) AF: 0.643 AC: 1361 AN: 2116

Alfa AF: 0.595 Hom.: 3652

Bravo AF: 0.620

Asia WGS AF: 0.572 AC: 1995 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.0
DANN	Benign	0.73
PhyloP100		-0.025
Mutation Taster		=100/0	polymorphism (auto)

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: rs9851548; hg19: chr3-137880695;