rs12334183

chr7-87572064-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001348946.2(ABCB1):c.287-1841A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,164 control chromosomes in the GnomAD database, including 4,366 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 0.22 (4366 hom., cov: 32)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.271

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB1	NM_001348946.2	c.287-1841A>G		intron_variant		ENST00000622132.5
ABCB1	NM_000927.5	c.287-1841A>G		intron_variant
ABCB1	NM_001348944.2	c.287-1841A>G		intron_variant
ABCB1	NM_001348945.2	c.497-1841A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB1	ENST00000622132.5	c.287-1841A>G		intron_variant		1	NM_001348946.2	P1
ABCB1	ENST00000265724.8	c.287-1841A>G		intron_variant		1		P1
ABCB1	ENST00000543898.5	c.287-1841A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34084 AN: 152046 Hom.: 4357 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.0600

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.153

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: 0.224 AC: 34143 AN: 152164 Hom.: 4366 Cov.: 32 AF XY: 0.220 AC XY: 16398 AN XY: 74394

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.0598

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.216

Alfa AF: 0.206 Hom.: 411

Bravo AF: 0.230

Asia WGS AF: 0.142 AC: 494 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.3
Dann	Benign	0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs12334183; hg19: chr7-87201380;