7-87519012-C-T

Variant names:

• chr7-87519012-C-T
• rs28401781
• NM_001348946.2:c.2927+314G>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.2927+314G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 394,554 control chromosomes in the GnomAD database, including 3,254 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 0.14 (1517 hom., cov: 32)
  • Exomes 𝑓: 0.12 (1737 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.554
• Publications: 13 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.2927+314G>A		intron_variant	Intron 23 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.3137+314G>A		intron_variant	Intron 27 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.2927+314G>A		intron_variant	Intron 24 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.2927+314G>A		intron_variant	Intron 25 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.2927+314G>A		intron_variant	Intron 23 of 27	1	NM_001348946.2	ENSP00000478255.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20536 AN: 152108 Hom.: 1507 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0593

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0506

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.115 AC: 27880 AN: 242328 Hom.: 1737 Cov.: 0 AF XY: 0.116 AC XY: 14727 AN XY: 126696

African (AFR) AF: 0.189 AC: 1510 AN: 7994

American (AMR) AF: 0.105 AC: 952 AN: 9098

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 1137 AN: 7556

East Asian (EAS) AF: 0.0510 AC: 759 AN: 14880

South Asian (SAS) AF: 0.130 AC: 3416 AN: 26232

European-Finnish (FIN) AF: 0.0535 AC: 666 AN: 12450

Middle Eastern (MID) AF: 0.107 AC: 117 AN: 1094

European-Non Finnish (NFE) AF: 0.118 AC: 17584 AN: 148734

Other (OTH) AF: 0.122 AC: 1739 AN: 14290

GnomAD4 genome AF: 0.135 AC: 20584 AN: 152226 Hom.: 1517 Cov.: 32 AF XY: 0.131 AC XY: 9781 AN XY: 74438

African (AFR) AF: 0.190 AC: 7881 AN: 41522

American (AMR) AF: 0.107 AC: 1641 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 510 AN: 3468

East Asian (EAS) AF: 0.0590 AC: 306 AN: 5184

South Asian (SAS) AF: 0.138 AC: 665 AN: 4824

European-Finnish (FIN) AF: 0.0506 AC: 537 AN: 10614

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

European-Non Finnish (NFE) AF: 0.125 AC: 8515 AN: 68016

Other (OTH) AF: 0.133 AC: 281 AN: 2112

Alfa AF: 0.131 Hom.: 2123

Bravo AF: 0.141

Asia WGS AF: 0.124 AC: 432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.4
DANN	Benign	0.68
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs28401781; hg19: chr7-87148328;