7-87512498-T-C

Variant names:

• chr7-87512498-T-C
• rs6949448
• NM_001348946.2:c.3282+2733A>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.3282+2733A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 152,056 control chromosomes in the GnomAD database, including 30,584 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 0.63 (30584 hom., cov: 32)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185
• Publications: 21 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.3282+2733A>G		intron_variant	Intron 25 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.3492+2733A>G		intron_variant	Intron 29 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.3282+2733A>G		intron_variant	Intron 26 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.3282+2733A>G		intron_variant	Intron 27 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.3282+2733A>G		intron_variant	Intron 25 of 27	1	NM_001348946.2	ENSP00000478255.1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94965 AN: 151938 Hom.: 30531 Cov.: 32

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.645

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.625 AC: 95077 AN: 152056 Hom.: 30584 Cov.: 32 AF XY: 0.620 AC XY: 46051 AN XY: 74316

African (AFR) AF: 0.786 AC: 32631 AN: 41502

American (AMR) AF: 0.599 AC: 9152 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2391 AN: 3470

East Asian (EAS) AF: 0.621 AC: 3211 AN: 5172

South Asian (SAS) AF: 0.428 AC: 2060 AN: 4818

European-Finnish (FIN) AF: 0.505 AC: 5330 AN: 10554

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.562 AC: 38170 AN: 67938

Other (OTH) AF: 0.644 AC: 1361 AN: 2114

Alfa AF: 0.585 Hom.: 45353

Bravo AF: 0.641

Asia WGS AF: 0.540 AC: 1877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.6
DANN	Benign	0.30
PhyloP100		0.18
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: rs6949448; hg19: chr7-87141814;