rs17149866

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001134405.2(RUNDC3B):​c.372+4971T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 152,360 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0031 ( 6 hom., cov: 32)

Consequence

RUNDC3B
NM_001134405.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.104

Publications

2 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BS1
Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00312 (475/152360) while in subpopulation EAS AF = 0.0492 (255/5188). AF 95% confidence interval is 0.0442. There are 6 homozygotes in GnomAd4. There are 249 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 6 Unknown gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RUNDC3BNM_001134405.2 linkc.372+4971T>C intron_variant Intron 3 of 10 ENST00000394654.4 NP_001127877.1 Q96NL0-5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RUNDC3BENST00000394654.4 linkc.372+4971T>C intron_variant Intron 3 of 10 2 NM_001134405.2 ENSP00000378149.3 Q96NL0-5

Frequencies

GnomAD3 genomes
AF:
0.00311
AC:
473
AN:
152240
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00190
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00635
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.0490
Gnomad SAS
AF:
0.00248
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.00478
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00312
AC:
475
AN:
152360
Hom.:
6
Cov.:
32
AF XY:
0.00334
AC XY:
249
AN XY:
74516
show subpopulations
African (AFR)
AF:
0.00190
AC:
79
AN:
41594
American (AMR)
AF:
0.00634
AC:
97
AN:
15306
Ashkenazi Jewish (ASJ)
AF:
0.000288
AC:
1
AN:
3472
East Asian (EAS)
AF:
0.0492
AC:
255
AN:
5188
South Asian (SAS)
AF:
0.00249
AC:
12
AN:
4828
European-Finnish (FIN)
AF:
0.0000941
AC:
1
AN:
10624
Middle Eastern (MID)
AF:
0.00340
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
0.000250
AC:
17
AN:
68026
Other (OTH)
AF:
0.00567
AC:
12
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
23
46
69
92
115
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000953
Hom.:
1
Bravo
AF:
0.00356
Asia WGS
AF:
0.0180
AC:
62
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
5.2
DANN
Benign
0.87
PhyloP100
0.10
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

Publications

Other links and lift over

dbSNP: rs17149866; hg19: chr7-87334841; API