7-87600185-T-C

Variant names:

• chr7-87600185-T-C
• rs2214102
• NM_001348946.2:c.-1A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001348945.2(ABCB1):​c.210A>G​(p.Gly70Gly) variant causes a synonymous 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). Synonymous variant affecting the same amino acid position (i.e. G70G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.95 (68389 hom., cov: 32)
  • Exomes 𝑓: 0.93 (627603 hom.)
• Consequence: ABCB1 NM_001348945.2 synonymous
• 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-1.73 with no splicing effect.
• 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_001348945.2. 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;