7-87572166-G-C

Variant names:

• chr7-87572166-G-C
• rs10260862
• NM_001348946.2:c.287-1943C>G

Variant summary

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

The NM_001348946.2(ABCB1):​c.287-1943C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 150,958 control chromosomes in the GnomAD database, including 4,346 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 0.23 (4346 hom., cov: 32)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298
• Publications: 8 publications found

Genes affected

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348946.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	NM_001348946.2	MANE Select	c.287-1943C>G		intron	N/A	NP_001335875.1
	ABCB1	NM_001348945.2		c.497-1943C>G		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.287-1943C>G		intron	N/A	NP_000918.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	ENST00000622132.5	TSL:1 MANE Select	c.287-1943C>G		intron	N/A	ENSP00000478255.1
	ABCB1	ENST00000265724.8	TSL:1	c.287-1943C>G		intron	N/A	ENSP00000265724.3
	ABCB1	ENST00000543898.5	TSL:5	c.287-1943C>G		intron	N/A	ENSP00000444095.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34032 AN: 150850 Hom.: 4337 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0599

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.226 AC: 34091 AN: 150958 Hom.: 4346 Cov.: 32 AF XY: 0.222 AC XY: 16368 AN XY: 73828

African (AFR) AF: 0.355 AC: 14355 AN: 40480

American (AMR) AF: 0.162 AC: 2471 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 772 AN: 3468

East Asian (EAS) AF: 0.0596 AC: 309 AN: 5182

South Asian (SAS) AF: 0.156 AC: 749 AN: 4810

European-Finnish (FIN) AF: 0.154 AC: 1631 AN: 10576

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13057 AN: 67926

Other (OTH) AF: 0.217 AC: 455 AN: 2100

Alfa AF: 0.169 Hom.: 1361

Bravo AF: 0.230

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.34
DANN	Benign	0.37
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: rs10260862; hg19: chr7-87201482;