7-87669552-A-G

Variant names:

• chr7-87669552-A-G
• rs2157930
• NM_001134405.2:c.238+18615A>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.238+18615A>G 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 152,154 control chromosomes in the GnomAD database, including 49,907 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 (49907 hom., cov: 32)
• Consequence: RUNDC3B NM_001134405.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 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.238+18615A>G		intron	N/A	NP_001127877.1	Q96NL0-5
	ABCB1	NM_001348945.2		c.-155+32089T>C		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.-331+43609T>C		intron	N/A	NP_000918.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNDC3B	ENST00000394654.4	TSL:2 MANE Select	c.238+18615A>G		intron	N/A	ENSP00000378149.3	Q96NL0-5
	ABCB1	ENST00000265724.8	TSL:1	c.-331+43609T>C		intron	N/A	ENSP00000265724.3	P08183-1
	RUNDC3B	ENST00000493037.5	TSL:1	c.238+18615A>G		intron	N/A	ENSP00000420394.1	Q96NL0-4

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122811 AN: 152036 Hom.: 49856 Cov.: 32

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.802

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

GnomAD4 genome AF: 0.808 AC: 122920 AN: 152154 Hom.: 49907 Cov.: 32 AF XY: 0.813 AC XY: 60491 AN XY: 74376

African (AFR) AF: 0.844 AC: 35043 AN: 41528

American (AMR) AF: 0.846 AC: 12929 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2708 AN: 3472

East Asian (EAS) AF: 0.987 AC: 5115 AN: 5180

South Asian (SAS) AF: 0.882 AC: 4259 AN: 4828

European-Finnish (FIN) AF: 0.803 AC: 8477 AN: 10558

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51891 AN: 67980

Other (OTH) AF: 0.802 AC: 1695 AN: 2114

Alfa AF: 0.801 Hom.: 9021

Bravo AF: 0.812

Asia WGS AF: 0.921 AC: 3202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.21
DANN	Benign	0.50
PhyloP100		-2.3
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: rs2157930; hg19: chr7-87298868;