chr7-87510000-A-G

Variant names:

• chr7-87510000-A-G
• rs4437575
• NM_001348946.2:c.3283-519T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001348946.2(ABCB1):​c.3283-519T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,940 control chromosomes in the GnomAD database, including 14,110 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 0.42 (14110 hom., cov: 31)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.3283-519T>C		intron_variant	Intron 25 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.3493-519T>C		intron_variant	Intron 29 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.3283-519T>C		intron_variant	Intron 26 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.3283-519T>C		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.3283-519T>C		intron_variant	Intron 25 of 27	1	NM_001348946.2	ENSP00000478255.1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64494 AN: 151822 Hom.: 14090 Cov.: 31

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.425 AC: 64554 AN: 151940 Hom.: 14110 Cov.: 31 AF XY: 0.422 AC XY: 31347 AN XY: 74258

African (AFR) AF: 0.399 AC: 16515 AN: 41430

American (AMR) AF: 0.462 AC: 7056 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2133 AN: 3464

East Asian (EAS) AF: 0.195 AC: 1009 AN: 5178

South Asian (SAS) AF: 0.312 AC: 1504 AN: 4814

European-Finnish (FIN) AF: 0.364 AC: 3836 AN: 10546

Middle Eastern (MID) AF: 0.441 AC: 128 AN: 290

European-Non Finnish (NFE) AF: 0.455 AC: 30905 AN: 67920

Other (OTH) AF: 0.471 AC: 995 AN: 2112

Alfa AF: 0.443 Hom.: 12887

Bravo AF: 0.431

Asia WGS AF: 0.273 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.2
DANN	Benign	0.83
PhyloP100		-0.024
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: rs4437575; hg19: chr7-87139316;