7-87536434-C-T

Variant names:

• chr7-87536434-C-T
• rs2235040
• NM_001348946.2:c.2481+24G>A

Variant summary

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

The NM_001348946.2(ABCB1):​c.2481+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,612,404 control chromosomes in the GnomAD database, including 13,436 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 (1266 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12170 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161
• Publications: 53 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.2481+24G>A		intron_variant	Intron 20 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.2691+24G>A		intron_variant	Intron 24 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.2481+24G>A		intron_variant	Intron 21 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.2481+24G>A		intron_variant	Intron 22 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.2481+24G>A		intron_variant	Intron 20 of 27	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.2481+24G>A		intron_variant	Intron 21 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.2289+24G>A		intron_variant	Intron 20 of 27	5		ENSP00000444095.1
ABCB1	ENST00000496821.5	n.109+24G>A		intron_variant	Intron 2 of 6	5

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19099 AN: 152020 Hom.: 1260 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0598

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0477

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.124

GnomAD2 exomes AF: 0.117 AC: 29470 AN: 251150 AF XY: 0.119

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.152

Gnomad EAS exome AF: 0.0575

Gnomad FIN exome AF: 0.0504

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.126 AC: 184150 AN: 1460266 Hom.: 12170 Cov.: 31 AF XY: 0.127 AC XY: 92181 AN XY: 726526

African (AFR) AF: 0.159 AC: 5305 AN: 33432

American (AMR) AF: 0.104 AC: 4632 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 4224 AN: 26114

East Asian (EAS) AF: 0.0546 AC: 2166 AN: 39672

South Asian (SAS) AF: 0.152 AC: 13118 AN: 86224

European-Finnish (FIN) AF: 0.0531 AC: 2833 AN: 53390

Middle Eastern (MID) AF: 0.125 AC: 722 AN: 5762

European-Non Finnish (NFE) AF: 0.129 AC: 143341 AN: 1110642

Other (OTH) AF: 0.129 AC: 7809 AN: 60328

GnomAD4 genome AF: 0.126 AC: 19136 AN: 152138 Hom.: 1266 Cov.: 32 AF XY: 0.123 AC XY: 9181 AN XY: 74390

African (AFR) AF: 0.153 AC: 6354 AN: 41492

American (AMR) AF: 0.109 AC: 1668 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 521 AN: 3470

East Asian (EAS) AF: 0.0596 AC: 309 AN: 5186

South Asian (SAS) AF: 0.151 AC: 728 AN: 4822

European-Finnish (FIN) AF: 0.0477 AC: 505 AN: 10590

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

European-Non Finnish (NFE) AF: 0.126 AC: 8539 AN: 67988

Other (OTH) AF: 0.125 AC: 264 AN: 2108

Alfa AF: 0.131 Hom.: 2908

Bravo AF: 0.130

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.3
DANN	Benign	0.76
PhyloP100		0.16
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: rs2235040; hg19: chr7-87165750;