7-87564281-G-A

Variant names:

• chr7-87564281-G-A
• rs4148734
• NM_001348946.2:c.702+1789C>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.702+1789C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 320,988 control chromosomes in the GnomAD database, including 11,284 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 (4677 hom., cov: 32)
  • Exomes 𝑓: 0.27 (6607 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600
• Publications: 12 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.308 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.702+1789C>T		intron	N/A	NP_001335875.1
	ABCB1	NM_001348945.2		c.912+1789C>T		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.702+1789C>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.702+1789C>T		intron	N/A	ENSP00000478255.1
	ABCB1	ENST00000265724.8	TSL:1	c.702+1789C>T		intron	N/A	ENSP00000265724.3
	ABCB1	ENST00000543898.5	TSL:5	c.510+1789C>T		intron	N/A	ENSP00000444095.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34170 AN: 152042 Hom.: 4673 Cov.: 32

Gnomad AFR AF: 0.0614

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.266 AC: 44961 AN: 168828 Hom.: 6607 AF XY: 0.256 AC XY: 24975 AN XY: 97506

African (AFR) AF: 0.0627 AC: 219 AN: 3492

American (AMR) AF: 0.293 AC: 2650 AN: 9056

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1407 AN: 4032

East Asian (EAS) AF: 0.154 AC: 769 AN: 4988

South Asian (SAS) AF: 0.165 AC: 5298 AN: 32168

European-Finnish (FIN) AF: 0.256 AC: 1888 AN: 7362

Middle Eastern (MID) AF: 0.270 AC: 601 AN: 2224

European-Non Finnish (NFE) AF: 0.308 AC: 29895 AN: 97102

Other (OTH) AF: 0.266 AC: 2234 AN: 8404

GnomAD4 genome AF: 0.225 AC: 34180 AN: 152160 Hom.: 4677 Cov.: 32 AF XY: 0.224 AC XY: 16642 AN XY: 74386

African (AFR) AF: 0.0611 AC: 2539 AN: 41522

American (AMR) AF: 0.316 AC: 4824 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1218 AN: 3472

East Asian (EAS) AF: 0.166 AC: 860 AN: 5172

South Asian (SAS) AF: 0.168 AC: 809 AN: 4828

European-Finnish (FIN) AF: 0.257 AC: 2721 AN: 10578

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20252 AN: 68000

Other (OTH) AF: 0.274 AC: 577 AN: 2108

Alfa AF: 0.268 Hom.: 11742

Bravo AF: 0.221

Asia WGS AF: 0.156 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.73
PhyloP100		-0.060
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: rs4148734; hg19: chr7-87193597; COSMIC: COSV55952168;