Genetic Variant RUNDC3B:c.123-1378G>T (chr7-87649444-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is . The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001134405.2(RUNDC3B):c.123-1378G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)

Consequence

RUNDC3B
NM_001134405.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.380

Publications

17 publications found

Variant links:

Genes affected

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

RUNDC3B links:

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]

ABCB1 Gene-Disease associations (from GenCC):

inflammatory bowel disease 13
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

ABCB1 links:

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new If you want to explore the variant's impact on the transcript NM_001134405.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RUNDC3B	NM_001134405.2	MANE Select	c.123-1378G>T	intron	N/A	NP_001127877.1	Q96NL0-5
ABCB1	NM_001348945.2		c.-154-46304C>A	intron	N/A	NP_001335874.1
ABCB1	NM_000927.5		c.-330-48366C>A	intron	N/A	NP_000918.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RUNDC3B	ENST00000394654.4	TSL:2 MANE Select	c.123-1378G>T	intron	N/A	ENSP00000378149.3	Q96NL0-5
ABCB1	ENST00000265724.8	TSL:1	c.-330-48366C>A	intron	N/A	ENSP00000265724.3	P08183-1
RUNDC3B	ENST00000493037.5	TSL:1	c.123-1378G>T	intron	N/A	ENSP00000420394.1	Q96NL0-4

Frequencies

GnomAD3 genomes

Cov.:

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.91

(source)

DANN

Benign

0.58

PhyloP100

-0.38

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over