rs3842

Variant names:

• chr7-87504050-T-C
• rs3842
• NM_001348946.2:c.*193A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-87504050-T-C
• chr7-87504050-T-A
• chr7-87504050-T-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.*193A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 651,800 control chromosomes in the GnomAD database, including 8,333 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 0.16 (1917 hom., cov: 32)
  • Exomes 𝑓: 0.15 (6416 hom.)
• Consequence: ABCB1 NM_001348946.2 3_prime_UTR
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -1.22
• Publications: 96 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 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.*193A>G		3_prime_UTR	Exon 28 of 28	NP_001335875.1	P08183-1
	ABCB1	NM_001348945.2		c.*193A>G		3_prime_UTR	Exon 32 of 32	NP_001335874.1
	ABCB1	NM_000927.5		c.*193A>G		3_prime_UTR	Exon 29 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.*193A>G		3_prime_UTR	Exon 28 of 28	ENSP00000478255.1	P08183-1
	ABCB1	ENST00000265724.8	TSL:1	c.*193A>G		3_prime_UTR	Exon 29 of 29	ENSP00000265724.3	P08183-1
	ABCB1	ENST00000488737.6	TSL:1	n.1678A>G		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23934 AN: 152026 Hom.: 1916 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.155 AC: 77370 AN: 499656 Hom.: 6416 Cov.: 6 AF XY: 0.155 AC XY: 40709 AN XY: 262136

African (AFR) AF: 0.182 AC: 2433 AN: 13378

American (AMR) AF: 0.139 AC: 2770 AN: 19878

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 2636 AN: 14470

East Asian (EAS) AF: 0.278 AC: 8626 AN: 31080

South Asian (SAS) AF: 0.170 AC: 7700 AN: 45260

European-Finnish (FIN) AF: 0.151 AC: 4646 AN: 30744

Middle Eastern (MID) AF: 0.195 AC: 406 AN: 2086

European-Non Finnish (NFE) AF: 0.139 AC: 43817 AN: 314992

Other (OTH) AF: 0.156 AC: 4336 AN: 27768

GnomAD4 genome AF: 0.157 AC: 23948 AN: 152144 Hom.: 1917 Cov.: 32 AF XY: 0.157 AC XY: 11686 AN XY: 74386

African (AFR) AF: 0.175 AC: 7273 AN: 41446

American (AMR) AF: 0.137 AC: 2092 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 665 AN: 3462

East Asian (EAS) AF: 0.276 AC: 1428 AN: 5182

South Asian (SAS) AF: 0.170 AC: 819 AN: 4816

European-Finnish (FIN) AF: 0.149 AC: 1578 AN: 10594

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.141 AC: 9622 AN: 68022

Other (OTH) AF: 0.151 AC: 319 AN: 2114

Alfa AF: 0.148 Hom.: 5036

Bravo AF: 0.159

Asia WGS AF: 0.212 AC: 737 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	-0.84
CADD	Benign	0.26
DANN	Benign	0.43
PhyloP100		-1.2
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: rs3842; hg19: chr7-87133366; COSMIC: COSV105051408; COSMIC: COSV105051408;