chr7-87595890-G-T

Variant names:

• chr7-87595890-G-T
• rs58898486
• NM_001348946.2:c.69-76C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001348946.2(ABCB1):​c.69-76C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00556 in 1,170,324 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

• Frequency:
  • Genomes: 𝑓 0.0052 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (31 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -0.654
• Publications: 2 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS2: High AC in GnomAd4 at 784 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.69-76C>A		intron_variant	Intron 2 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.279-76C>A		intron_variant	Intron 6 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.69-76C>A		intron_variant	Intron 3 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.69-76C>A		intron_variant	Intron 4 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.69-76C>A		intron_variant	Intron 2 of 27	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.69-76C>A		intron_variant	Intron 3 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.69-76C>A		intron_variant	Intron 3 of 27	5		ENSP00000444095.1
ABCB1	ENST00000416177.1	c.69-76C>A		intron_variant	Intron 4 of 5	5		ENSP00000399419.1

Frequencies

GnomAD3 genomes AF: 0.00517 AC: 785 AN: 151858 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00387

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.0206

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00641

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.00562 AC: 5719 AN: 1018348 Hom.: 31 AF XY: 0.00545 AC XY: 2857 AN XY: 524326

African (AFR) AF: 0.000794 AC: 19 AN: 23944

American (AMR) AF: 0.00365 AC: 152 AN: 41668

Ashkenazi Jewish (ASJ) AF: 0.00178 AC: 41 AN: 22978

East Asian (EAS) AF: 0.00 AC: 0 AN: 35534

South Asian (SAS) AF: 0.00201 AC: 149 AN: 73950

European-Finnish (FIN) AF: 0.0174 AC: 848 AN: 48816

Middle Eastern (MID) AF: 0.00174 AC: 7 AN: 4016

European-Non Finnish (NFE) AF: 0.00589 AC: 4253 AN: 722300

Other (OTH) AF: 0.00554 AC: 250 AN: 45142

GnomAD4 genome AF: 0.00516 AC: 784 AN: 151976 Hom.: 5 Cov.: 32 AF XY: 0.00574 AC XY: 426 AN XY: 74278

African (AFR) AF: 0.00106 AC: 44 AN: 41504

American (AMR) AF: 0.00387 AC: 59 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4810

European-Finnish (FIN) AF: 0.0206 AC: 218 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00639 AC: 434 AN: 67882

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00545 Hom.: 1

Bravo AF: 0.00429

Asia WGS AF: 0.000581 AC: 2 AN: 3456

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Tramadol response Other:1

Apr 28, 2018

Bruce Budowle Laboratory, University of North Texas Health Science Center

Significance: drug response

Review Status: no assertion criteria provided

Collection Method: research

- T:M1 = postmortem ratio or tramadol to O-desmethyltramadol; t-MP = model-based clustered metabolizer phenotype inferred from T:M1

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.17
DANN	Benign	0.48
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism

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: rs58898486; hg19: chr7-87225206;