3-138161853-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBR1	NM_016216.4	c.*36T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000260803.9	NP_057300.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBR1	ENST00000260803	c.*36T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_016216.4	ENSP00000260803.4

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

GnomAD3 exomes AF: 0.648 AC: 156163 AN: 241066 Hom.: 51039 AF XY: 0.652 AC XY: 84663 AN XY: 129842

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 SAS exome AF: 0.605

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

Gnomad4 AFR exome AF: 0.485

Gnomad4 AMR exome AF: 0.636

Gnomad4 ASJ exome AF: 0.695

Gnomad4 EAS exome AF: 0.561

Gnomad4 SAS exome AF: 0.608

Gnomad4 FIN exome AF: 0.669

Gnomad4 NFE exome AF: 0.697

Gnomad4 OTH exome AF: 0.665

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

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.683

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.687

Gnomad4 OTH AF: 0.643

Alfa AF: 0.599 Hom.: 3557

Bravo AF: 0.620

Asia WGS AF: 0.572 AC: 1995 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.0
DANN	Benign	0.73

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

Other links and lift over

dbSNP: rs9851548; hg19: chr3-137880695;