7-87591900-A-G

Variant names:

• chr7-87591900-A-G
• rs1858923
• NM_001348946.2:c.117+3866T>C

Variant summary

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

The NM_001348946.2(ABCB1):​c.117+3866T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 152,012 control chromosomes in the GnomAD database, including 12,593 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 0.38 (12593 hom., cov: 31)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 18 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.625 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.117+3866T>C		intron	N/A	NP_001335875.1
	ABCB1	NM_001348945.2		c.327+3866T>C		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.117+3866T>C		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.117+3866T>C		intron	N/A	ENSP00000478255.1
	ABCB1	ENST00000265724.8	TSL:1	c.117+3866T>C		intron	N/A	ENSP00000265724.3
	ABCB1	ENST00000543898.5	TSL:5	c.117+3866T>C		intron	N/A	ENSP00000444095.1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57298 AN: 151894 Hom.: 12603 Cov.: 31

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.377 AC: 57284 AN: 152012 Hom.: 12593 Cov.: 31 AF XY: 0.383 AC XY: 28428 AN XY: 74308

African (AFR) AF: 0.144 AC: 5963 AN: 41482

American (AMR) AF: 0.379 AC: 5787 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1325 AN: 3466

East Asian (EAS) AF: 0.479 AC: 2473 AN: 5168

South Asian (SAS) AF: 0.644 AC: 3108 AN: 4824

European-Finnish (FIN) AF: 0.491 AC: 5169 AN: 10534

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.473 AC: 32133 AN: 67952

Other (OTH) AF: 0.371 AC: 783 AN: 2112

Alfa AF: 0.442 Hom.: 59855

Bravo AF: 0.358

Asia WGS AF: 0.535 AC: 1858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.5
DANN	Benign	0.22
PhyloP100		1.5
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: rs1858923; hg19: chr7-87221216;