7-87531733-T-C

Variant names:

• chr7-87531733-T-C
• rs4148739
• NM_001348946.2:c.2482-236A>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.2482-236A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 498,352 control chromosomes in the GnomAD database, including 4,195 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1386 hom., cov: 32)
  • Exomes 𝑓: 0.12 (2809 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175
• Publications: 23 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	NM_001348946.2	MANE Select	c.2482-236A>G		intron	N/A	NP_001335875.1
	ABCB1	NM_001348945.2		c.2692-236A>G		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.2482-236A>G		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.2482-236A>G		intron	N/A	ENSP00000478255.1
	ABCB1	ENST00000265724.8	TSL:1	c.2482-236A>G		intron	N/A	ENSP00000265724.3
	ABCB1	ENST00000543898.5	TSL:5	c.2290-236A>G		intron	N/A	ENSP00000444095.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19864 AN: 152018 Hom.: 1378 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0584

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0470

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.123 AC: 42618 AN: 346216 Hom.: 2809 Cov.: 3 AF XY: 0.126 AC XY: 23199 AN XY: 184212

African (AFR) AF: 0.178 AC: 1871 AN: 10482

American (AMR) AF: 0.115 AC: 1676 AN: 14560

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 1750 AN: 10648

East Asian (EAS) AF: 0.0561 AC: 1275 AN: 22746

South Asian (SAS) AF: 0.153 AC: 5953 AN: 38842

European-Finnish (FIN) AF: 0.0566 AC: 990 AN: 17494

Middle Eastern (MID) AF: 0.118 AC: 174 AN: 1480

European-Non Finnish (NFE) AF: 0.126 AC: 26360 AN: 209910

Other (OTH) AF: 0.128 AC: 2569 AN: 20054

GnomAD4 genome AF: 0.131 AC: 19907 AN: 152136 Hom.: 1386 Cov.: 32 AF XY: 0.128 AC XY: 9512 AN XY: 74384

African (AFR) AF: 0.171 AC: 7090 AN: 41496

American (AMR) AF: 0.111 AC: 1699 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 521 AN: 3468

East Asian (EAS) AF: 0.0582 AC: 301 AN: 5172

South Asian (SAS) AF: 0.152 AC: 732 AN: 4824

European-Finnish (FIN) AF: 0.0470 AC: 498 AN: 10596

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8548 AN: 67994

Other (OTH) AF: 0.128 AC: 270 AN: 2112

Alfa AF: 0.131 Hom.: 3667

Bravo AF: 0.136

Asia WGS AF: 0.123 AC: 427 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.3
DANN	Benign	0.38
PhyloP100		-0.17
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: rs4148739; hg19: chr7-87161049;