rs4148727

Positions:

• chr7-87713450-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134405.2(RUNDC3B):​c.458+2795A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0485 in 152,192 control chromosomes in the GnomAD database, including 270 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

• Frequency:
  • Genomes: 𝑓 0.048 (270 hom., cov: 32)
  • Exomes 𝑓: 0.063 (0 hom.)
• Consequence: RUNDC3B NM_001134405.2 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: 0.0550

Genes affected

RUNDC3B (HGNC:30286): (RUN domain containing 3B)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUNDC3B	NM_001134405.2	c.458+2795A>G		intron_variant		ENST00000394654.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNDC3B	ENST00000394654.4	c.458+2795A>G		intron_variant		2	NM_001134405.2	P1

Frequencies

GnomAD3 genomes AF: 0.0485 AC: 7379 AN: 152058 Hom.: 270 Cov.: 32

Gnomad AFR AF: 0.0806

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0568

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.0973

Gnomad SAS AF: 0.0358

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0265

Gnomad OTH AF: 0.0522

GnomAD4 exome AF: 0.0625 AC: 1 AN: 16 Hom.: 0 AF XY: 0.0833 AC XY: 1 AN XY: 12

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.100

GnomAD4 genome AF: 0.0485 AC: 7377 AN: 152176 Hom.: 270 Cov.: 32 AF XY: 0.0490 AC XY: 3643 AN XY: 74402

Gnomad4 AFR AF: 0.0805

Gnomad4 AMR AF: 0.0567

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.0968

Gnomad4 SAS AF: 0.0354

Gnomad4 FIN AF: 0.0369

Gnomad4 NFE AF: 0.0265

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0343 Hom.: 75

Bravo AF: 0.0532

Asia WGS AF: 0.0600 AC: 207 AN: 3478

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Tramadol response Other:1

drug response, no assertion criteria provided

research

Bruce Budowle Laboratory, University of North Texas Health Science Center

Apr 28, 2018

- T:M1 = postmortem ratio or tramadol to O-desmethyltramadol; t-MP = model-based clustered metabolizer phenotype inferred from T:M1

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.64
DANN	Benign	0.65

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: rs4148727; hg19: chr7-87342766;