rs2235047

Positions:

• chr7-87509216-A-C
• chr7-87509216-A-G

Variant summary

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

The NM_001348946.2(ABCB1):​c.3489+59T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0458 in 1,568,672 control chromosomes in the GnomAD database, including 6,628 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 0.088 (1344 hom., cov: 32)
  • Exomes 𝑓: 0.041 (5284 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.62

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.3489+59T>G		intron_variant		ENST00000622132.5	NP_001335875.1
ABCB1	NM_000927.5	c.3489+59T>G		intron_variant			NP_000918.2
ABCB1	NM_001348944.2	c.3489+59T>G		intron_variant			NP_001335873.1
ABCB1	NM_001348945.2	c.3699+59T>G		intron_variant			NP_001335874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.3489+59T>G		intron_variant		1	NM_001348946.2	ENSP00000478255	P1

Frequencies

GnomAD3 genomes AF: 0.0878 AC: 13349 AN: 152052 Hom.: 1342 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.0790

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.0955

Gnomad FIN AF: 0.0206

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0185

Gnomad OTH AF: 0.0793

GnomAD4 exome AF: 0.0413 AC: 58484 AN: 1416502 Hom.: 5284 AF XY: 0.0417 AC XY: 29479 AN XY: 707424

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.0323

Gnomad4 EAS exome AF: 0.421

Gnomad4 SAS exome AF: 0.0840

Gnomad4 FIN exome AF: 0.0266

Gnomad4 NFE exome AF: 0.0158

Gnomad4 OTH exome AF: 0.0592

GnomAD4 genome AF: 0.0878 AC: 13364 AN: 152170 Hom.: 1344 Cov.: 32 AF XY: 0.0900 AC XY: 6699 AN XY: 74414

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.0792

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.0947

Gnomad4 FIN AF: 0.0206

Gnomad4 NFE AF: 0.0185

Gnomad4 OTH AF: 0.0823

Alfa AF: 0.0311 Hom.: 325

Bravo AF: 0.100

Asia WGS AF: 0.226 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.1
DANN	Benign	0.59

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: rs2235047; hg19: chr7-87138532; COSMIC: COSV55964648; COSMIC: COSV55964648;