rs2235074

Variant names:

• chr7-87595730-G-A
• rs2235074
• NM_001348946.2:c.117+36C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-87595730-G-A
• chr7-87595730-G-T

Variant summary

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

The ENST00000622132.5(ABCB1):​c.117+36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0445 in 1,516,832 control chromosomes in the GnomAD database, including 1,890 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 0.063 (390 hom., cov: 32)
  • Exomes 𝑓: 0.043 (1500 hom.)
• Consequence: ABCB1 ENST00000622132.5 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: 0.518
• Publications: 15 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000622132.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	NM_001348946.2	MANE Select	c.117+36C>T		intron	N/A	NP_001335875.1
	ABCB1	NM_001348945.2		c.327+36C>T		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.117+36C>T		intron	N/A	NP_000918.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	ENST00000622132.5	TSL:1 MANE Select	c.117+36C>T		intron	N/A	ENSP00000478255.1
	ABCB1	ENST00000265724.8	TSL:1	c.117+36C>T		intron	N/A	ENSP00000265724.3
	ABCB1	ENST00000543898.5	TSL:5	c.117+36C>T		intron	N/A	ENSP00000444095.1

Frequencies

GnomAD3 genomes AF: 0.0623 AC: 9461 AN: 151802 Hom.: 385 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0378

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.0506

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.0345

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0408

Gnomad OTH AF: 0.0671

GnomAD2 exomes AF: 0.0430 AC: 10674 AN: 248138 AF XY: 0.0409

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.0384

Gnomad ASJ exome AF: 0.0259

Gnomad EAS exome AF: 0.0469

Gnomad FIN exome AF: 0.0375

Gnomad NFE exome AF: 0.0394

Gnomad OTH exome AF: 0.0399

GnomAD4 exome AF: 0.0425 AC: 58040 AN: 1364912 Hom.: 1500 Cov.: 22 AF XY: 0.0418 AC XY: 28600 AN XY: 684114

African (AFR) AF: 0.130 AC: 4113 AN: 31552

American (AMR) AF: 0.0399 AC: 1764 AN: 44254

Ashkenazi Jewish (ASJ) AF: 0.0264 AC: 671 AN: 25460

East Asian (EAS) AF: 0.0603 AC: 2355 AN: 39066

South Asian (SAS) AF: 0.0267 AC: 2232 AN: 83580

European-Finnish (FIN) AF: 0.0382 AC: 2034 AN: 53250

Middle Eastern (MID) AF: 0.0535 AC: 297 AN: 5552

European-Non Finnish (NFE) AF: 0.0409 AC: 41932 AN: 1025066

Other (OTH) AF: 0.0462 AC: 2642 AN: 57132

GnomAD4 genome AF: 0.0625 AC: 9498 AN: 151920 Hom.: 390 Cov.: 32 AF XY: 0.0609 AC XY: 4521 AN XY: 74294

African (AFR) AF: 0.124 AC: 5130 AN: 41436

American (AMR) AF: 0.0378 AC: 576 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 76 AN: 3468

East Asian (EAS) AF: 0.0507 AC: 263 AN: 5188

South Asian (SAS) AF: 0.0317 AC: 153 AN: 4826

European-Finnish (FIN) AF: 0.0345 AC: 365 AN: 10570

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0408 AC: 2768 AN: 67860

Other (OTH) AF: 0.0674 AC: 142 AN: 2108

Alfa AF: 0.0440 Hom.: 256

Bravo AF: 0.0650

Asia WGS AF: 0.0460 AC: 163 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.83
CADD	Benign	5.4
DANN	Benign	0.80
PhyloP100		0.52
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: rs2235074; hg19: chr7-87225046;