7-87540386-A-C

Variant names:

• chr7-87540386-A-C
• rs12720066
• NM_001348946.2:c.2319+971T>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.2319+971T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 152,318 control chromosomes in the GnomAD database, including 153 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 0.039 (153 hom., cov: 32)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.839
• Publications: 18 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.2319+971T>G		intron_variant	Intron 18 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.2529+971T>G		intron_variant	Intron 22 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.2319+971T>G		intron_variant	Intron 19 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.2319+971T>G		intron_variant	Intron 20 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.2319+971T>G		intron_variant	Intron 18 of 27	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.2319+971T>G		intron_variant	Intron 19 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.2127+971T>G		intron_variant	Intron 18 of 27	5		ENSP00000444095.1

Frequencies

GnomAD3 genomes AF: 0.0387 AC: 5896 AN: 152200 Hom.: 153 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.0398

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0602

Gnomad OTH AF: 0.0492

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

GnomAD4 genome AF: 0.0387 AC: 5896 AN: 152318 Hom.: 153 Cov.: 32 AF XY: 0.0369 AC XY: 2748 AN XY: 74486

African (AFR) AF: 0.0103 AC: 428 AN: 41584

American (AMR) AF: 0.0484 AC: 740 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0398 AC: 138 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0151 AC: 73 AN: 4832

European-Finnish (FIN) AF: 0.0203 AC: 215 AN: 10614

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0602 AC: 4096 AN: 68016

Other (OTH) AF: 0.0487 AC: 103 AN: 2114

Alfa AF: 0.0505 Hom.: 439

Bravo AF: 0.0402

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.4
DANN	Benign	0.71
PhyloP100		0.84
Mutation Taster		=100/0	polymorphism

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: rs12720066; hg19: chr7-87169702;