rs10233247

Positions:

• chr7-87642522-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.123-8300A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.05 in 152,174 control chromosomes in the GnomAD database, including 294 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 0.050 (294 hom., cov: 32)
• Consequence: RUNDC3B NM_001134405.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUNDC3B	NM_001134405.2	c.123-8300A>G		intron_variant		ENST00000394654.4	NP_001127877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNDC3B	ENST00000394654.4	c.123-8300A>G		intron_variant		2	NM_001134405.2	ENSP00000378149	P1

Frequencies

GnomAD3 genomes AF: 0.0501 AC: 7613 AN: 152056 Hom.: 294 Cov.: 32

Gnomad AFR AF: 0.0815

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0575

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.0366

Gnomad FIN AF: 0.0368

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0265

Gnomad OTH AF: 0.0527

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

GnomAD4 genome AF: 0.0500 AC: 7610 AN: 152174 Hom.: 294 Cov.: 32 AF XY: 0.0505 AC XY: 3759 AN XY: 74414

Gnomad4 AFR AF: 0.0814

Gnomad4 AMR AF: 0.0574

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.0362

Gnomad4 FIN AF: 0.0368

Gnomad4 NFE AF: 0.0265

Gnomad4 OTH AF: 0.0521

Alfa AF: 0.0329 Hom.: 106

Bravo AF: 0.0548

Asia WGS AF: 0.0800 AC: 275 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.5
DANN	Benign	0.83

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: rs10233247; hg19: chr7-87271838; COSMIC: COSV55958398;