rs10267099

Positions:

• chr7-87649444-G-A
• chr7-87649444-G-C
• chr7-87649444-G-T

Variant summary

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

The NM_001134405.2(RUNDC3B):​c.123-1378G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,082 control chromosomes in the GnomAD database, including 49,879 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 0.81 (49879 hom., cov: 31)
• Consequence: RUNDC3B NM_001134405.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUNDC3B	NM_001134405.2	c.123-1378G>A		intron_variant		ENST00000394654.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNDC3B	ENST00000394654.4	c.123-1378G>A		intron_variant		2	NM_001134405.2	P1

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122726 AN: 151964 Hom.: 49827 Cov.: 31

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.803

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

GnomAD4 genome AF: 0.808 AC: 122836 AN: 152082 Hom.: 49879 Cov.: 31 AF XY: 0.813 AC XY: 60437 AN XY: 74330

Gnomad4 AFR AF: 0.844

Gnomad4 AMR AF: 0.845

Gnomad4 ASJ AF: 0.780

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.882

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.803

Alfa AF: 0.776 Hom.: 78949

Bravo AF: 0.812

Asia WGS AF: 0.921 AC: 3202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.63

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: rs10267099; hg19: chr7-87278760;