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. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001348946.2(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 NM_001348946.2 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: 0.518

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.117+36C>T		intron_variant	Intron 3 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.327+36C>T		intron_variant	Intron 7 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.117+36C>T		intron_variant	Intron 4 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.117+36C>T		intron_variant	Intron 5 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.117+36C>T		intron_variant	Intron 3 of 27	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.117+36C>T		intron_variant	Intron 4 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.117+36C>T		intron_variant	Intron 4 of 27	5		ENSP00000444095.1
ABCB1	ENST00000416177.1	c.117+36C>T		intron_variant	Intron 5 of 5	5		ENSP00000399419.1

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

GnomAD3 exomes AF: 0.0430 AC: 10674 AN: 248138 Hom.: 324 AF XY: 0.0409 AC XY: 5487 AN XY: 134138

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 SAS exome AF: 0.0272

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

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.0399

Gnomad4 ASJ exome AF: 0.0264

Gnomad4 EAS exome AF: 0.0603

Gnomad4 SAS exome AF: 0.0267

Gnomad4 FIN exome AF: 0.0382

Gnomad4 NFE exome AF: 0.0409

Gnomad4 OTH exome AF: 0.0462

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

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.0378

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.0507

Gnomad4 SAS AF: 0.0317

Gnomad4 FIN AF: 0.0345

Gnomad4 NFE AF: 0.0408

Gnomad4 OTH AF: 0.0674

Alfa AF: 0.0430 Hom.: 216

Bravo AF: 0.0650

Asia WGS AF: 0.0460 AC: 163 AN: 3478

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Tramadol response Other:1

Apr 28, 2018

Bruce Budowle Laboratory, University of North Texas Health Science Center

Significance: drug response

Review Status: no assertion criteria provided

Collection Method: research

- T:M1 = postmortem ratio or tramadol to O-desmethyltramadol; t-MP = model-based clustered metabolizer phenotype inferred from T:M1

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs2235074; hg19: chr7-87225046; COSMIC: COSV55954081;