7-87536434-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.79).
• 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/exons	MANE	UniProt
ABCB1	NM_001348946.2	c.2481+24G>A		intron_variant		ENST00000622132.5
ABCB1	NM_000927.5	c.2481+24G>A		intron_variant
ABCB1	NM_001348944.2	c.2481+24G>A		intron_variant
ABCB1	NM_001348945.2	c.2691+24G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB1	ENST00000622132.5	c.2481+24G>A		intron_variant		1	NM_001348946.2	P1
ABCB1	ENST00000265724.8	c.2481+24G>A		intron_variant		1		P1
ABCB1	ENST00000543898.5	c.2289+24G>A		intron_variant		5
ABCB1	ENST00000496821.5	n.109+24G>A		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes AF: 0.117 AC: 29470 AN: 251150 Hom.: 1942 AF XY: 0.119 AC XY: 16196 AN XY: 135736

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 SAS exome AF: 0.155

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

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.0546

Gnomad4 SAS exome AF: 0.152

Gnomad4 FIN exome AF: 0.0531

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.129

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

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.0596

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.0477

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.125

Alfa AF: 0.132 Hom.: 1902

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

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: rs2235040; hg19: chr7-87165750;