rs17327442

Variant names:

• chr7-87583674-T-A
• rs17327442
• NM_001348946.2:c.286+1838A>T

Variant summary

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

The NM_001348946.2(ABCB1):​c.286+1838A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,128 control chromosomes in the GnomAD database, including 2,944 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 0.19 (2944 hom., cov: 32)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959
• Publications: 11 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.255 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.286+1838A>T		intron	N/A	NP_001335875.1
	ABCB1	NM_001348945.2		c.496+1838A>T		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.286+1838A>T		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.286+1838A>T		intron	N/A	ENSP00000478255.1
	ABCB1	ENST00000265724.8	TSL:1	c.286+1838A>T		intron	N/A	ENSP00000265724.3
	ABCB1	ENST00000543898.5	TSL:5	c.286+1838A>T		intron	N/A	ENSP00000444095.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28260 AN: 152010 Hom.: 2931 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.186 AC: 28314 AN: 152128 Hom.: 2944 Cov.: 32 AF XY: 0.187 AC XY: 13926 AN XY: 74356

African (AFR) AF: 0.255 AC: 10572 AN: 41504

American (AMR) AF: 0.262 AC: 3997 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 733 AN: 3468

East Asian (EAS) AF: 0.120 AC: 619 AN: 5172

South Asian (SAS) AF: 0.140 AC: 677 AN: 4820

European-Finnish (FIN) AF: 0.119 AC: 1262 AN: 10592

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9879 AN: 67986

Other (OTH) AF: 0.201 AC: 423 AN: 2106

Alfa AF: 0.167 Hom.: 324

Bravo AF: 0.198

Asia WGS AF: 0.145 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.41
DANN	Benign	0.83
PhyloP100		-0.96
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: rs17327442; hg19: chr7-87212990;