rs2235023

Variant names:

• chr7-87561136-C-T
• rs2235023
• NM_001348946.2:c.827+127G>A

Variant summary

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

The NM_001348946.2(ABCB1):​c.827+127G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0803 in 1,075,792 control chromosomes in the GnomAD database, including 5,170 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 0.12 (1794 hom., cov: 33)
  • Exomes 𝑓: 0.073 (3376 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 17 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.827+127G>A		intron_variant	Intron 8 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.1037+127G>A		intron_variant	Intron 12 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.827+127G>A		intron_variant	Intron 9 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.827+127G>A		intron_variant	Intron 10 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.827+127G>A		intron_variant	Intron 8 of 27	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.827+127G>A		intron_variant	Intron 9 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.635+127G>A		intron_variant	Intron 8 of 27	5		ENSP00000444095.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18910 AN: 152036 Hom.: 1778 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0611

Gnomad ASJ AF: 0.0818

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0159

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0728

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.0730 AC: 67414 AN: 923638 Hom.: 3376 AF XY: 0.0706 AC XY: 33128 AN XY: 469498

African (AFR) AF: 0.278 AC: 5827 AN: 20954

American (AMR) AF: 0.0429 AC: 972 AN: 22680

Ashkenazi Jewish (ASJ) AF: 0.0755 AC: 1370 AN: 18152

East Asian (EAS) AF: 0.000116 AC: 4 AN: 34554

South Asian (SAS) AF: 0.0158 AC: 917 AN: 57906

European-Finnish (FIN) AF: 0.127 AC: 5475 AN: 43184

Middle Eastern (MID) AF: 0.0845 AC: 310 AN: 3670

European-Non Finnish (NFE) AF: 0.0723 AC: 49292 AN: 681390

Other (OTH) AF: 0.0789 AC: 3247 AN: 41148

GnomAD4 genome AF: 0.125 AC: 18968 AN: 152154 Hom.: 1794 Cov.: 33 AF XY: 0.123 AC XY: 9163 AN XY: 74396

African (AFR) AF: 0.266 AC: 11015 AN: 41478

American (AMR) AF: 0.0609 AC: 932 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0818 AC: 284 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0159 AC: 77 AN: 4830

European-Finnish (FIN) AF: 0.135 AC: 1426 AN: 10562

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0728 AC: 4949 AN: 68006

Other (OTH) AF: 0.106 AC: 224 AN: 2112

Alfa AF: 0.0901 Hom.: 2311

Bravo AF: 0.127

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.21
DANN	Benign	0.47
PhyloP100		-1.2
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: rs2235023; hg19: chr7-87190452;