7-87585798-A-C

Variant names:

• chr7-87585798-A-C
• rs1211152
• NM_001348946.2:c.118-118T>G

Variant summary

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

The NM_001348946.2(ABCB1):​c.118-118T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.942 in 1,007,268 control chromosomes in the GnomAD database, including 447,216 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 0.96 (69578 hom., cov: 32)
  • Exomes 𝑓: 0.94 (377638 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -1.54
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 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.118-118T>G		intron	N/A	NP_001335875.1	P08183-1
	ABCB1	NM_001348945.2		c.328-118T>G		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.118-118T>G		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.118-118T>G		intron	N/A	ENSP00000478255.1	P08183-1
	ABCB1	ENST00000265724.8	TSL:1	c.118-118T>G		intron	N/A	ENSP00000265724.3	P08183-1
	ABCB1	ENST00000890305.1		c.118-118T>G		intron	N/A	ENSP00000560364.1

Frequencies

GnomAD3 genomes AF: 0.955 AC: 145374 AN: 152172 Hom.: 69514 Cov.: 32

Gnomad AFR AF: 0.987

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.979

Gnomad ASJ AF: 0.986

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.994

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.929

Gnomad OTH AF: 0.961

GnomAD4 exome AF: 0.939 AC: 803069 AN: 854978 Hom.: 377638 AF XY: 0.942 AC XY: 414572 AN XY: 440244

African (AFR) AF: 0.988 AC: 20639 AN: 20880

American (AMR) AF: 0.984 AC: 32002 AN: 32538

Ashkenazi Jewish (ASJ) AF: 0.982 AC: 20022 AN: 20386

East Asian (EAS) AF: 1.00 AC: 33337 AN: 33338

South Asian (SAS) AF: 0.992 AC: 64067 AN: 64580

European-Finnish (FIN) AF: 0.916 AC: 30852 AN: 33692

Middle Eastern (MID) AF: 0.991 AC: 4171 AN: 4210

European-Non Finnish (NFE) AF: 0.925 AC: 559805 AN: 605270

Other (OTH) AF: 0.952 AC: 38174 AN: 40084

GnomAD4 genome AF: 0.955 AC: 145497 AN: 152290 Hom.: 69578 Cov.: 32 AF XY: 0.958 AC XY: 71327 AN XY: 74464

African (AFR) AF: 0.987 AC: 41052 AN: 41572

American (AMR) AF: 0.979 AC: 14977 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.986 AC: 3423 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5177 AN: 5180

South Asian (SAS) AF: 0.994 AC: 4792 AN: 4822

European-Finnish (FIN) AF: 0.919 AC: 9750 AN: 10606

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.929 AC: 63168 AN: 68018

Other (OTH) AF: 0.961 AC: 2034 AN: 2116

Alfa AF: 0.945 Hom.: 102841

Bravo AF: 0.961

Asia WGS AF: 0.995 AC: 3461 AN: 3478

ClinVar

ClinVar submissions

Significance: drug response

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Tramadol response (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.39
DANN	Benign	0.75
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1211152; hg19: chr7-87215114;