rs4148727

Variant names:

• chr7-87713450-A-G
• rs4148727
• NM_001134405.2:c.458+2795A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

Genes affected

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

ABCB1 (HGNC:40): (ATP binding cassette subfamily B member 1) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity. It is responsible for decreased drug accumulation in multidrug-resistant cells and often mediates the development of resistance to anticancer drugs. This protein also functions as a transporter in the blood-brain barrier. Mutations in this gene are associated with colchicine resistance and Inflammatory bowel disease 13. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134405.2. 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
	RUNDC3B	NM_001134405.2	MANE Select	c.458+2795A>G		intron	N/A	NP_001127877.1	Q96NL0-5
	RUNDC3B	NM_138290.3		c.509+2795A>G		intron	N/A	NP_612147.1	Q96NL0-1
	RUNDC3B	NM_001394224.1		c.509+2795A>G		intron	N/A	NP_001381153.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNDC3B	ENST00000394654.4	TSL:2 MANE Select	c.458+2795A>G		intron	N/A	ENSP00000378149.3	Q96NL0-5
	RUNDC3B	ENST00000493037.5	TSL:1	c.458+2795A>G		intron	N/A	ENSP00000420394.1	Q96NL0-4
	RUNDC3B	ENST00000338056.7	TSL:2	c.509+2795A>G		intron	N/A	ENSP00000337732.3	Q96NL0-1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.100 AC: 1 AN: 10

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0805 AC: 3341 AN: 41502

American (AMR) AF: 0.0567 AC: 866 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 136 AN: 3470

East Asian (EAS) AF: 0.0968 AC: 501 AN: 5176

South Asian (SAS) AF: 0.0354 AC: 171 AN: 4824

European-Finnish (FIN) AF: 0.0369 AC: 391 AN: 10610

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0265 AC: 1802 AN: 68006

Other (OTH) AF: 0.0511 AC: 108 AN: 2112

Alfa AF: 0.0343 Hom.: 86

Bravo AF: 0.0532

Asia WGS AF: 0.0600 AC: 207 AN: 3478

ClinVar

ClinVar submissions

Significance: drug response

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Tramadol response (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.64
DANN	Benign	0.65
PhyloP100		0.055
PromoterAI		0.027	Neutral
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: rs4148727; hg19: chr7-87342766;