7-87552533-G-T

Variant names:

• chr7-87552533-G-T
• rs3789244
• NM_001348946.2:c.999+1228C>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.999+1228C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 151,568 control chromosomes in the GnomAD database, including 28,364 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 0.60 (28364 hom., cov: 29)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 11 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348946.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	NM_001348946.2	MANE Select	c.999+1228C>A		intron	N/A	NP_001335875.1	P08183-1
	ABCB1	NM_001348945.2		c.1209+1228C>A		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.999+1228C>A		intron	N/A	NP_000918.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	ENST00000622132.5	TSL:1 MANE Select	c.999+1228C>A		intron	N/A	ENSP00000478255.1	P08183-1
	ABCB1	ENST00000265724.8	TSL:1	c.999+1228C>A		intron	N/A	ENSP00000265724.3	P08183-1
	ABCB1	ENST00000890305.1		c.999+1228C>A		intron	N/A	ENSP00000560364.1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91266 AN: 151450 Hom.: 28311 Cov.: 29

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.603 AC: 91389 AN: 151568 Hom.: 28364 Cov.: 29 AF XY: 0.596 AC XY: 44154 AN XY: 74062

African (AFR) AF: 0.752 AC: 31069 AN: 41332

American (AMR) AF: 0.567 AC: 8626 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2195 AN: 3464

East Asian (EAS) AF: 0.364 AC: 1871 AN: 5136

South Asian (SAS) AF: 0.401 AC: 1925 AN: 4804

European-Finnish (FIN) AF: 0.514 AC: 5377 AN: 10466

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38272 AN: 67840

Other (OTH) AF: 0.610 AC: 1285 AN: 2106

Alfa AF: 0.493 Hom.: 1600

Bravo AF: 0.614

Asia WGS AF: 0.426 AC: 1488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.9
DANN	Benign	0.54
PhyloP100		-0.13
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: rs3789244; hg19: chr7-87181849;