rs10264856

Variant names:

• chr7-87633265-G-A
• rs10264856
• NM_001134405.2:c.122+4320G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001348945.2(ABCB1):​c.-154-30125C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,152 control chromosomes in the GnomAD database, including 3,174 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 0.16 (3174 hom., cov: 32)
• Consequence: ABCB1 NM_001348945.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302
• Publications: 15 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 (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348945.2. 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.122+4320G>A		intron	N/A	NP_001127877.1
	ABCB1	NM_001348945.2		c.-154-30125C>T		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.-330-32187C>T		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.122+4320G>A		intron	N/A	ENSP00000378149.3
	ABCB1	ENST00000265724.8	TSL:1	c.-330-32187C>T		intron	N/A	ENSP00000265724.3
	RUNDC3B	ENST00000493037.5	TSL:1	c.122+4320G>A		intron	N/A	ENSP00000420394.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23856 AN: 152034 Hom.: 3153 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0668

Gnomad FIN AF: 0.0713

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0674

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.157 AC: 23917 AN: 152152 Hom.: 3174 Cov.: 32 AF XY: 0.155 AC XY: 11502 AN XY: 74380

African (AFR) AF: 0.366 AC: 15167 AN: 41446

American (AMR) AF: 0.114 AC: 1744 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0637 AC: 221 AN: 3472

East Asian (EAS) AF: 0.141 AC: 728 AN: 5180

South Asian (SAS) AF: 0.0665 AC: 321 AN: 4828

European-Finnish (FIN) AF: 0.0713 AC: 756 AN: 10600

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0674 AC: 4585 AN: 68010

Other (OTH) AF: 0.148 AC: 311 AN: 2108

Alfa AF: 0.0887 Hom.: 1157

Bravo AF: 0.171

Asia WGS AF: 0.115 AC: 402 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	2.2
DANN	Benign	0.54
PhyloP100		0.30
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: rs10264856; hg19: chr7-87262581;