NM_001348946.2:c.3283-2377C>G

Variant names:

• chr7-87511858-G-C
• rs1002205
• NM_001348946.2:c.3283-2377C>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.3283-2377C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,176 control chromosomes in the GnomAD database, including 2,452 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 (2452 hom., cov: 32)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.3283-2377C>G		intron_variant	Intron 25 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.3493-2377C>G		intron_variant	Intron 29 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.3283-2377C>G		intron_variant	Intron 26 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.3283-2377C>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.3283-2377C>G		intron_variant	Intron 25 of 27	1	NM_001348946.2	ENSP00000478255.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21356 AN: 152058 Hom.: 2446 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0571

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0537

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.140 AC: 21378 AN: 152176 Hom.: 2452 Cov.: 32 AF XY: 0.142 AC XY: 10558 AN XY: 74406

African (AFR) AF: 0.282 AC: 11680 AN: 41466

American (AMR) AF: 0.123 AC: 1879 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 387 AN: 3472

East Asian (EAS) AF: 0.396 AC: 2041 AN: 5160

South Asian (SAS) AF: 0.146 AC: 705 AN: 4818

European-Finnish (FIN) AF: 0.0571 AC: 606 AN: 10610

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0537 AC: 3650 AN: 68030

Other (OTH) AF: 0.138 AC: 292 AN: 2114

Alfa AF: 0.0175 Hom.: 10

Bravo AF: 0.156

Asia WGS AF: 0.240 AC: 833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.68
PhyloP100		0.27
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: rs1002205; hg19: chr7-87141174;