chr7-87570248-C-A

Variant names:

• chr7-87570248-C-A
• rs2235015
• NM_001348946.2:c.287-25G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001348946.2(ABCB1):​c.287-25G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,594,280 control chromosomes in the GnomAD database, including 31,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4369 hom., cov: 33)
  • Exomes 𝑓: 0.19 (27471 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: -1.26
• Publications: 66 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-87570248-C-A is Benign according to our data. Variant chr7-87570248-C-A is described in ClinVar as Benign. ClinVar VariationId is 675797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	NM_001348946.2	MANE Select	c.287-25G>T		intron	N/A	NP_001335875.1	P08183-1
	ABCB1	NM_001348945.2		c.497-25G>T		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.287-25G>T		intron	N/A	NP_000918.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	ENST00000622132.5	TSL:1 MANE Select	c.287-25G>T		intron	N/A	ENSP00000478255.1	P08183-1
	ABCB1	ENST00000265724.8	TSL:1	c.287-25G>T		intron	N/A	ENSP00000265724.3	P08183-1
	ABCB1	ENST00000890305.1		c.287-25G>T		intron	N/A	ENSP00000560364.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34097 AN: 151940 Hom.: 4361 Cov.: 33

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0598

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.213

GnomAD2 exomes AF: 0.178 AC: 44574 AN: 250346 AF XY: 0.176

Gnomad AFR exome AF: 0.353

Gnomad AMR exome AF: 0.136

Gnomad ASJ exome AF: 0.222

Gnomad EAS exome AF: 0.0580

Gnomad FIN exome AF: 0.152

Gnomad NFE exome AF: 0.190

Gnomad OTH exome AF: 0.191

GnomAD4 exome AF: 0.189 AC: 273207 AN: 1442222 Hom.: 27471 Cov.: 28 AF XY: 0.188 AC XY: 135176 AN XY: 718684

African (AFR) AF: 0.364 AC: 12009 AN: 33000

American (AMR) AF: 0.139 AC: 6224 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 5960 AN: 25976

East Asian (EAS) AF: 0.0550 AC: 2174 AN: 39496

South Asian (SAS) AF: 0.159 AC: 13652 AN: 85836

European-Finnish (FIN) AF: 0.155 AC: 8114 AN: 52420

Middle Eastern (MID) AF: 0.196 AC: 1129 AN: 5746

European-Non Finnish (NFE) AF: 0.194 AC: 212206 AN: 1095342

Other (OTH) AF: 0.197 AC: 11739 AN: 59726

GnomAD4 genome AF: 0.225 AC: 34154 AN: 152058 Hom.: 4369 Cov.: 33 AF XY: 0.221 AC XY: 16407 AN XY: 74336

African (AFR) AF: 0.347 AC: 14387 AN: 41448

American (AMR) AF: 0.162 AC: 2482 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 772 AN: 3468

East Asian (EAS) AF: 0.0595 AC: 309 AN: 5190

South Asian (SAS) AF: 0.155 AC: 749 AN: 4818

European-Finnish (FIN) AF: 0.153 AC: 1619 AN: 10558

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13085 AN: 67976

Other (OTH) AF: 0.216 AC: 455 AN: 2108

Alfa AF: 0.199 Hom.: 9277

Bravo AF: 0.231

Asia WGS AF: 0.141 AC: 491 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	-	Tramadol response (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.72
DANN	Benign	0.73
PhyloP100		-1.3
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: rs2235015; hg19: chr7-87199564;