chr3-138162030-C-T

Variant names:

• chr3-138162030-C-T
• rs6803524
• NM_016216.4:c.1494G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_016216.4(DBR1):​c.1494G>A​(p.Glu498Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,614,152 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0093 (27 hom., cov: 32)
  • Exomes 𝑓: 0.00091 (15 hom.)
• Consequence: DBR1 NM_016216.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.250
• Publications: 1 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=-0.85).
• BP6: Variant 3-138162030-C-T is Benign according to our data. Variant chr3-138162030-C-T is described in ClinVar as Benign. ClinVar VariationId is 717204.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.25 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0093 (1416/152264) while in subpopulation AFR AF = 0.033 (1370/41546). AF 95% confidence interval is 0.0315. There are 27 homozygotes in GnomAd4. There are 655 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

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.1494G>A	p.Glu498Glu	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.1494G>A	p.Glu498Glu	synonymous	Exon 8 of 8	ENSP00000260803.4	Q9UK59-1
	DBR1	ENST00000698924.1		c.1413G>A	p.Glu471Glu	synonymous	Exon 7 of 7	ENSP00000514035.1	A0A8V8TNX0
	DBR1	ENST00000698922.1		c.1269G>A	p.Glu423Glu	synonymous	Exon 7 of 7	ENSP00000514033.1	A0A8V8TMF7

Frequencies

GnomAD3 genomes AF: 0.00923 AC: 1405 AN: 152146 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0328

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00237 AC: 595 AN: 251482 AF XY: 0.00175

Gnomad AFR exome AF: 0.0344

Gnomad AMR exome AF: 0.000723

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000908 AC: 1327 AN: 1461888 Hom.: 15 Cov.: 37 AF XY: 0.000803 AC XY: 584 AN XY: 727246

African (AFR) AF: 0.0339 AC: 1134 AN: 33480

American (AMR) AF: 0.000850 AC: 38 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1112006

Other (OTH) AF: 0.00189 AC: 114 AN: 60396

GnomAD4 genome AF: 0.00930 AC: 1416 AN: 152264 Hom.: 27 Cov.: 32 AF XY: 0.00880 AC XY: 655 AN XY: 74460

African (AFR) AF: 0.0330 AC: 1370 AN: 41546

American (AMR) AF: 0.00177 AC: 27 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68024

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00462 Hom.: 7

Bravo AF: 0.0102

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.56
DANN	Benign	0.24
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism

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: rs6803524; hg19: chr3-137880872;