NM_001348946.2:c.-1A>G

Variant names:

• chr7-87600185-T-C
• rs2214102
• NM_001348946.2:c.-1A>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.-1A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 1,613,460 control chromosomes in the GnomAD database, including 695,992 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 0.95 (68389 hom., cov: 32)
  • Exomes 𝑓: 0.93 (627603 hom.)
• Consequence: ABCB1 NM_001348946.2 5_prime_UTR
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -1.73
• Publications: 56 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.-1A>G		5_prime_UTR	Exon 2 of 28	NP_001335875.1	P08183-1
	ABCB1	NM_001348945.2		c.210A>G	p.Gly70Gly	synonymous	Exon 6 of 32	NP_001335874.1
	ABCB1	NM_000927.5		c.-1A>G		5_prime_UTR	Exon 3 of 29	NP_000918.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	ENST00000622132.5	TSL:1 MANE Select	c.-1A>G		5_prime_UTR	Exon 2 of 28	ENSP00000478255.1	P08183-1
	ABCB1	ENST00000265724.8	TSL:1	c.-1A>G		5_prime_UTR	Exon 3 of 29	ENSP00000265724.3	P08183-1
	ABCB1	ENST00000890305.1		c.-1A>G		5_prime_UTR	Exon 1 of 27	ENSP00000560364.1

Frequencies

GnomAD3 genomes AF: 0.947 AC: 144120 AN: 152202 Hom.: 68324 Cov.: 32

Gnomad AFR AF: 0.985

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.972

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.991

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.952

GnomAD2 exomes AF: 0.946 AC: 237728 AN: 251178 AF XY: 0.946

Gnomad AFR exome AF: 0.986

Gnomad AMR exome AF: 0.977

Gnomad ASJ exome AF: 0.966

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.910

Gnomad NFE exome AF: 0.917

Gnomad OTH exome AF: 0.946

GnomAD4 exome AF: 0.926 AC: 1353616 AN: 1461140 Hom.: 627603 Cov.: 46 AF XY: 0.929 AC XY: 674929 AN XY: 726886

African (AFR) AF: 0.988 AC: 33072 AN: 33476

American (AMR) AF: 0.976 AC: 43652 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.967 AC: 25283 AN: 26136

East Asian (EAS) AF: 1.00 AC: 39697 AN: 39700

South Asian (SAS) AF: 0.988 AC: 85217 AN: 86218

European-Finnish (FIN) AF: 0.908 AC: 48464 AN: 53396

Middle Eastern (MID) AF: 0.977 AC: 5635 AN: 5766

European-Non Finnish (NFE) AF: 0.914 AC: 1015842 AN: 1111366

Other (OTH) AF: 0.940 AC: 56754 AN: 60364

GnomAD4 genome AF: 0.947 AC: 144244 AN: 152320 Hom.: 68389 Cov.: 32 AF XY: 0.950 AC XY: 70749 AN XY: 74488

African (AFR) AF: 0.985 AC: 40954 AN: 41570

American (AMR) AF: 0.972 AC: 14865 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.965 AC: 3352 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5186 AN: 5190

South Asian (SAS) AF: 0.991 AC: 4784 AN: 4826

European-Finnish (FIN) AF: 0.909 AC: 9638 AN: 10608

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.917 AC: 62371 AN: 68040

Other (OTH) AF: 0.952 AC: 2013 AN: 2114

Alfa AF: 0.932 Hom.: 239345

Bravo AF: 0.953

Asia WGS AF: 0.992 AC: 3449 AN: 3478

EpiCase AF: 0.925

EpiControl AF: 0.924

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	-0.76
CADD	Benign	7.0
DANN	Benign	0.56
PhyloP100		-1.7
Mutation Taster		=300/0	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: rs2214102; hg19: chr7-87229501;